\r\n\tIn conclusion, this book is intended for Engineers for research in the domains of speech signals and ECG denoising and also in the domain of image denoising. Many mathematical tools can be used for speech enhancement, ECG Denoising, and Image Denoising. Among those tools, we can mention wavelets, Empirical Mode Decomposition, Total Variation Denoising, Non-Local Means (NLMS), Kalman Filtering, Wiener Filtering, Deep Learning, etc.
",isbn:"978-1-83768-030-6",printIsbn:"978-1-83768-029-0",pdfIsbn:"978-1-83768-031-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"9885534183ae520bcc63a91d4d083390",bookSignature:"Dr. Mourad Talbi",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11943.jpg",keywords:"Speech Enhancement, Thresholding, Signal to Noise Ratio, Wavelets, ECG Denoising, Empirical Mode Decomposition, Total Variation Denoising, Image Denoising, SNR, Non-local Means (NLMS), Kalman Filtering, Wiener Filtering",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 11th 2022",dateEndSecondStepPublish:"June 8th 2022",dateEndThirdStepPublish:"August 7th 2022",dateEndFourthStepPublish:"October 26th 2022",dateEndFifthStepPublish:"December 25th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"14 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Assistant Professor Mourad Talbi obtained his Ph.D. in Electronics at the Faculty of Sciences of Tunis, Tunisia. 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1. Introduction to radioisotopes and radiopharmaceuticals
Scientist has discovered that earth contains many elements with varying configuration. These elements with varying configuration are called isotopes. Isotopes are atoms with same atomic number with varying atomic weight. Isotopes can be divided into two parts depending on the ability to emit radiation. One that does not emit radiations is called stable isotopes and other are called unstable isotopes. Unstable isotopes emit radiations to achieve a more stable configuration. These are called as radioisotopes. Instability of radioisotopes is due to presence of unstable combination of neutron and proton in their atoms and nucleus contains excess of energy. This characteristic of radioisotopes can be natural or instability can be created artificially by changing the atoms. Naturally radioisotope is uranium-238 and it accounts to 0.7% of total naturally occurring isotopes. Artificial radioisotopes are fluorine and molybdenum which are produced artificially by using cyclotrons and nuclear reactors respectively. Presently there are around 3800 radioisotopes out of which 200 radioisotopes are being used. Among the isotopes that are used most of them are of artificial origin. Artificial radioisotopes are primarily made by two methods as mentioned above i.e. through nuclear reactor and by cyclotron. By nuclear reactor neutrons are introduced into the nucleus of atom whereas in case of cyclotron proton are introduced. To become stable radioisotopes emits alpha or beta particle along with electromagnetic radiation of gamma rays. This phenomenon is called as radioactive decay. These radioisotopes have variety of uses, when they are used in the field of pharmaceuticals they are termed as radiopharmaceuticals.
1.1 Radiopharmaceuticals
These are radioactive medicines that can be given by oral, intravenous or interstitial route to treat or diagnose malignancy. Administration of these drugs is done in the presence of specialist called radio pharmacist. These radioactive medicines have the ability to destroy cancerous cell by emitting radiation when it reaches its target cell. Radiopharmaceuticals for treatment and diagnosis of cancers associated with thyroid, brain, bones or lymphoma already been discovered.
In addition to treatment radiopharmaceuticals are also used for the purpose of diagnosis. The drugs used for diagnosis are called as tracers. The radiation of diagnostic radiopharmaceuticals is smaller as compared to radiation emitted by radiopharmaceuticals used for treatment. Radiopharmaceuticals are either single isotopes or sometimes the isotopes are combined with a kit [1]. The kit is prepackaging of ingredients which are sterile and are meant for preparation of radiopharmaceuticals. They are combination of substances such as antioxidant, buffer, reductant and ligands that are when combined with the radioisotopes produces the resultant product. Kits are very beneficial as they are not in contact with the outer environment so there is no chance of any contamination [2].
1.2 Technetium 99m
The isotope that is used for the purpose of labeling of kits used for diagnosis is technetium 99m abbreviated as 99mTc (Figure 1). It radiates only gamma radiation that is compatible with gamma camera. 99mTc also has the property of binding with the tracers. Advantage of technetium is that it has smaller biological half-life and better renal clearance for the unabsorbed radiopharmaceuticals that helps in getting a better quality of image from the absorbed ones. The dose of technetium depends on the kit, the organ on which it has to be used for imaging and on the test to be performed [3]. Determination of dose for children is very crucial as the cells are in dividing states so sensitivity towards radiation can be higher, organ size body ratio also varies to greater extent in comparison with adult. So in case of children a balanced level of administration is required [4].
Figure 1.
Chemical structure of technetium 99m.
Different kit labeled with 99mTc used for imaging of different organs is mentioned below.
1.2.1 Bone
For detection of the areas that are metabolizing the bones kits with bisphosphonates are used. Scan of bone is done by injecting radiopharmaceuticals into the peripheral vein of patient and then after 3 h imaging is done so that within the three hours the bisphosphonates will get incorporated into the osteoblast cells.
1.2.2 Kidney
For the imaging of kidney, there are three radiopharmaceuticals, namely
Mag-3; mertiatide is used for the purpose of determining the blood flow to the kidney and for graphically presenting the renal function. Mag-3 has a clearance of 94% after 3 h that helps in getting better quality of image and the exposure of patient to the radiation is also lower. DTPA; pentetate is used to determining rate of glomerular filtration during chemotherapy of kidney. Lastly DMSA; succimer is used a tool for studying morphology of renal cortex and ectopic kidney.
1.2.3 Brain
Kit used for the check the blood flow within the brain after conditions like epilepsy, migraine or Alzheimer’s disease or stroke of brain contains 99mTc-labeled exametazime. This is product of lipophilic origin without any charge on it and it penetrates better through blood brain barrier. It takes around one minute after injection for it to reach brain and up to 7% reaches the brain.
1.2.4 Heart
For cardiac imaging, two 99mTc-labeled are tetrofosmin and sestamibi which are employed to ascertain the degree to which myocardial infarction is severe and also help to point out the regions of cardiac ischemia. Images are collected at the state of rest and after stressed activity of cardiac cells. This injection are administered when patient must have consumed any kind of fatty meal. This helps in hepatobiliary clearance of administered radiopharmaceuticals thus aid in getting better image. But it should not be administered when patients has consumed some drugs such as nitrates or calcium channel blockers.
1.2.5 Lungs
In case of lungs scan it is used for the purpose of diagnosis of any kind of embolism in pulmonary tract. Lung scan be of two types perfusion scan or ventilation scan. First, one 99mTc-labeled macroaggregated albumin is injected in the peripheral vein, which is then carried to the pulmonary artery system. It does not get absorbed rather it gets distributed evenly in the capillary bed and helps in diagnosis. Where blood flow is good there will be larger number of particles giving out radiation, whereas where there will less perfusion then less particles will be seen.
In case of ventilation scan, patient is made to inhale radioactive substance such as krypton or 99mTc-labeled DTPA aerosol. Image is obtained where air is seen circulating in lungs [5].
1.3 Adverse reactions
The most common adverse reaction associated with radiopharmaceuticals is sweating, nausea, dry mouth and rashes.
2. Recent approaches of injectable radiopharmaceuticals as nuclear medicine for imaging and therapy
The aim of this chapter is to explain about advancements the injectable of biomaterials or radiopharmaceuticals origin used in molecular imaging, therapy and clinical diagnosis. On the basis of intrinsic radiation form, radioisotopes can be divided into following type namely gamma (γ) ray emitters, beta (positron β+ or electron β−) particles emitters and alpha (α) particles emitters or their combinations. In clinical practice and pre-clinical animal studies, mostly used radionuclides are gamma ray emitters like Technetium-99m (99mTc), Iodine-123 (123I) and Galium-67 (67Ga), Positron-emitting radionuclides namely Fluorine-18 (18F), Oxygen-15 (15O), Carbon-11 (11C) and Zirconium 89 (89Zr). Some β-emitters are Rhenium-186/Rhenium-188 (186Re/188Re), Strontium-89 (89Sr), and Yttrium-90 (90Y). Examples of therapeutic α-emitters are Actinium-225 (225Ac), Bismuth-213 (213Bi) and Astatine-211 (211At) [6]. The injected radiopharmaceuticals can be in simple ionic form or in carrier complex form. Carrier complex has better targeting ability for certain tissues and cells and pathways of disease. These are some radioisotopes used for imaging are as follows (Table 1):
In case of imaging, the major focus was development of 11C, 18F or 68Ga radiopharmaceuticals to be used in positron emission tomography (PET) and 99mTc-labeled agents for the used in single-photon emission computed tomography (SPECT) [8]. The merits associated with nuclear medicine are many such as it is noninvasive, it gives better in identifying exact region of tumor and beneficial for diagnosis of challenging diseases [9, 10]. In addition to this there is better quantitative analysis which is achieved with a numerous tools available. For example standard uptake values (SUVs) are taken in PET and in case of SPECT it is compared in vivo distribution of the injected materials [11]. There are some common nuclides mentioned in Table 2 which are used in radiation therapy are:
This content focuses on the developments in field of imaging technology in relevance to imaging of radionuclide therapy.
2.1 SPECT and scintigraphy
This type of decay of radionuclides determines about the modality for imaging. Planar scintigraphy or SPECT is used for imaging of 177Lu, 90Y, and 131I-which are used for radionuclide therapy. These emit γ-photons (or bremsstrahlung photons), which can be imaged by a γ-camera.
2.1.1 Current status
SPECT/CT systems which are used nowadays are used for both planar and tomographic imaging. Planar imaging is for acquiring whole-body images in when there is limitation of time. SPECT is meant for acquiring 3-dimensional data of structures which would otherwise overlap on each another on planar images.
Quantitative analysis of SPECT images is determined by converting the acquired counts in terms of distribution of absorbed dose (in Gy), which is beneficial for planning and dosimetry of therapy involving radionuclide. In clinical practice scatter correction is also implemented and is generally performed employing the triple-energy window method [13]. Quality of image can be enhanced by using resolution recovery. It is performed by characterizing the shape of the point-spread function accurately, that depends its distance from the camera and there is rotational variation due to the hexagonal pattern of the collimator septa. Reconstruction algorithm can be incorporated with point-spread function model subsequently [14].
Effects like scatter, blurring and attenuation which degrades image can be corrected to some extent, Although SPECT images can be degraded by partial-volume effects and quantification errors.
2.2 PET
18F-FDG PET is used for many PET studies that are in the field of clinical practice and is employed for staging and follow-up post radionuclide therapy. However, PET has application in planning of treatment, dosimetry, and assessment of treatment after radionuclide therapies.
2.2.1 Current status
Similar to SPECT quantitative PET is also used for correction techniques. Correction of attenuation for PET can be done through determination of the sonogram associated with attenuation correction, which works on the basis of co-registered CT data. Scatter correction is often done with single-scatter simulation method in clinical practice [15]. Correction for random counts is often done using delayed-event subtraction [16].
The difference in time between annihilation photons gives information regarding location of the annihilation and also about the line of response. Now time-of-flight information in the reconstruction at the time of back projection step enhances image quality. The availability of time-of-flight estimation has opened the opportunities for low positron abundance imaging isotopes like 90Y.
As intrinsic resolution of PET detectors are not freely available, so shape of the point-spread function is used to improve the quality of images by incorporating it during reconstruction method. This is called as resolution recovery.
When there are high count rate radiation detection systems does not work properly due to dead-time effect caused by pulse pile-up. Because of these Dead-time losses are corrected regularly.
2.2.2 Advances
There are better quality of PET images with enhanced resolutions and sensitivity due to regular improvement in the instrument which provides precise determination of the SUV [17].
2.3 PET/MRI
The advantages of PET/MRI over PET/CT are higher soft-tissue contrast that is essential for planning of treatment, dosimetry, and assessment post radionuclide therapies. Additionally, for accurate dosimetry it is beneficial as it provides the simultaneous coregisteration of MR images. Also, MRI can be employed for determining the tolerable dose with least organ damaging activity of radionuclide. Along with it anatomic and molecular images acquisition provides better motion correction.
Integrating of PET and MRI modalities is challenging as there will be interference between both the modalities. For instance, photomultiplier tubes that are present in PET detectors malfunction in magnetic fields exerted by MRI. In addition to this, PET module affects the radiofrequency signal associated with MRI [18]. Due to this, the first generation of PET/MRI systems modalities were separated. Integration of PET detectors and MR scanner has been done to obtain PET and MR images simultaneously. Detector systems is avalanche photodiodes types or SiPMs types which are not sensitive to magnetic field. The simultaneous measurement provides better 4-dimensional acquisitions because of spatial agreement of PET and MRI data.
Disadvantages associated with PET/MRI are high costs and the ferromagnetic metallic implants which are used is contradictory to MRI. In addition to this it’s challenging to correct attenuation of PET/MRI. For dosimetry it is essential to have accurate attenuation correction. As CT images are electron-density images and MR images are proton density image, CT image are better suited for attenuation correction. But MR images can be used for attenuation correction by using techniques such as segmentation-based or template- or atlas-based which derives electron density information from MR images [19]. Alternatively, estimation of the attenuation maps can be done by employing algorithms which uses the time-of-flight emission or transmission data [20].
2.4 Future perspectives
2.4.1 Simultaneous X-ray and nuclear imaging
Till today there are no real-time hybrid imaging modalities that can merge nuclear and anatomic for interventional purposes. Fluoroscopic imaging in combination with real-time nuclear imaging gives physicians with valuable information during procedures like as 90Y liver radio embolization by image distribution of the radionuclide in association with the anatomy and the interventional instruments that enhances therapeutic efficiency. Image of same field can be seen by arranging X-ray tube, an X-ray detector, and a γ-camera in a single line [21].
3. Different types and applications of radioisotopes for imaging and therapy
S. no
Radioisotopes
Uses
1.
Calcium-47
Important aid to biomedical researchers studying cellular functions and bone formation in mammals
2.
Caesuim-137
Used to treat cancerous tumors and to measure correct dosages of radioactive pharmaceuticals
3.
Chromium-51
Used in research in red blood cells survival studies
4.
Cobalt-57
Used as a tracer to diagnose pernicious anemia
5.
Cobalt-60
Used to sterilize surgical instruments and used in cancer treatment, food irradiation and radiography
6.
Copper-67
When injected to monoclonal antibodies into a cancer patient, helps the antibodies bind to and destroy the tumor
7.
Gallium-67
Used in medical diagnosis
8.
Iodine-123
Widely used to diagnose thyroid disorders and other metabolic disorders including brain functions
9.
Iodine-125
Major diagnostic tool used in clinical test and to diagnose thyroid disorders. Also used in biomedical research
10.
Iodine-129
Used to check some radioactivity counters in in-vitro diagnostic testing laboratories
11.
Iodine-131
Used to treat thyroid disorders (Graves’ disease)
12.
Iridium-192
In brachytherapy/tumor irradiation
13.
Phosphorous-32 and Phosphorous-33
Used in molecular biology and genetics research
14.
Technetium-99m
Most widely used radioactive pharmaceutical for diagnostic studies in nuclear medicine. Different chemical forms are used for brain, bone, liver, spleen and kidney imaging
15.
Uranium-234
Used in dental fixtures like crowns and dentures to provide a natural color and brightness
16.
Xenon-133
Used in nuclear medicine for lung ventilation and blood flow studies
3.1 Applications
Applications of different radioactive isotopes in nuclear medicine are [22]:
Cobalt-60 is used in radiation therapy for prevention of cancer.
Iodine-131 has been used for locating brain tumors, monitor activity of cardiac, liver and thyroid cells.
Carbon-14 used for determining metabolic changes happening in patients of diabetes, gout and anemia.
Carbon-11 is used to monitor organs during PET scan by tagging it into glucose.
Thallium-201 has been in use for determining damage in heart tissue, detection of tumors.
Technetium-99m act as radiotracer in medical diagnostics for obtaining the image of organs and study of blood flow. It also crucial for locating brain tumors and damaged heart cells [23].
4. Advantages and disadvantages of injectable radiopharmaceuticals
4.1 Properties of all radiopharmaceutical injectable
It should be sterile and free from Pyrogens. Sterility means absence of any living things even the spores or any related substances that can develop into something living. Culturing samples with special growth media is most common way to perform the assessment of sterility. Pyrogens are endotoxins that have the ability to cause pyrexia. They cannot be destroyed by autoclave and cannot be filtered. Testing for Pyrogens can be tested by using the rabbit test or the Limulus amebocyte lysate (LAL) test.
The isotonicity of injectable drug should be equal to 0.9% NaCl solution, and the pH should be 7.5.
In case of radioactive substance dose calibration should be done and it should be within ±10% of the prescribed dose. This calibration provides assurance that dose is as low as possible and it gives high quality image.
4.1.1 Advantages
It is used for diagnosis and treatment of patients.
It is commonly used to cure to cancers and can treat many other sites of disease.
Treats tumor such as bone metastasis.
Provide faster onset of relief from pain.
Single dose is effective for some patients.
Tests of nuclear medicine can be done on children.
Nuclear medicine procedure less costly and painless.
Nuclear medicine procedures are safe with no side effects [24].
4.1.2 Disadvantages
Some allergic reactions can be seen.
Risk of radiation is associated.
Myelosuppression may occur before chemotherapy.
Prolonged in convenience and discomfort can be experienced by patients due to administration of multiple fraction.
Nuclear medicine tests cannot use for pregnant women because of potential risk to unborn babies.
5. Theranostics
Theranostics is a combination of two words Therapeutics and diagnostics. This is an emerging field of medicine where drugs and/or techniques are used in combination for treatment as well as treatment. It’s a game changer as it provides diagnosis as well as therapy in single combination. It is economical as well as less time consuming. It uses PET scan to target tumor receptors which are present in tumor cell. If it is found in the cells radioactive drug is used to treat it. There are not much clinical trials found related to use of application of theranostics in prostate cancer by Australian Medicines Regulator—The Therapeutic Goods Administration (TGA) [25] (Figure 2).
Figure 2.
Theranostics working on tumor cell.
5.1 Theranostics: Nuclear Medicine Imaging
The Nuclear Medicine Imaging approach is revolutionized by use theranostics [targeted therapeutic (Rx) + companion diagnostic (DX)] to establish tools for specific molecular targeting. It provides personalized treatment plan for the patient by targeting specific targets. Various department of nuclear science can utilize theranostic agents [26].
5.2 Therapeutic bullets
Theranostics takes advantage of biological pathways specific to any system of human body to acquire diagnostic images. These images enhances the probability that the targeted therapeutic dosing of radiation that will only target disease part sparing the healthy one.
5.3 Nuclear Medicine Imaging
In past 100 years a similar kind of model for neuroendocrine tumors has been developed that has used radionuclide gallium-68. This PET radiotracer has been chelated to DOTA-octreotate and used for diagnosis of tumor with higher sensitivity compared to Indium-111 octreotide imaging.
The disease of patients can be determined by using the gallium-68 DOTA-TATE for targeting the somatostatin receptor volume and having image using hybrid scanner like PET-CT (Positron Emission Tomography-Computer Tomography). Lutetium Octreotate Therapy is a radiopharmaceuticals which emits beta radiation is available in 5 medical centers in north America and European medical centers [27].
Some of the milestones in the field of theranostics becoming personalized medicine are as follows:
Lutetium PSMA therapy for metastatic or treatment-resistant prostate cancer
Yttrium-90 SIRT therapy for liver cancer
Iodine-131 therapy for thyrotoxicosis and thyroid cancer
Radium-223 therapy for metastatic prostate cancer in bones
Yttrium-90 radiosynovectomy therapy for inflammatory synovitis of joints
Theranostics targeted therapy is difficult in case of cancer treatment due to heterogeneity of cancer cells. Ibritumomab a monoclonal antibody detects B-cells and produces the beta/alpha-emitting radiometal for destroying the lymphoma. SPECT imaging confirms distribution of antibody in the body. The indium-111 combined with radionuclide yttrium-90 transports beta particles for killing the B-cells [28] (Figure 3).
Figure 3.
Theranostics in cancer targeting and treatment.
5.4 Theranostics: Zevalin therapy
Zevalin therapy is used for determining the indications for relapsed or refractory, low-grade or follicular, B-cell non-Hodgkin’s lymphoma. Zevalin is FDA approved for the treatment of relapsed or refractory low-grade follicular. In the year 2008 Zevalin was approved as the first-line drug for follicular lymphoma in the European Union.
5.4.1 Characteristics
5.4.1.1 Diagnostic component
The diagnostic component contains radiotracer, a contrast agent molecule, and a particulate system with either inherent physical property like optical, magnetic property or an acquired physical property such as, contrast enhanced ultrasound property or combinations of both. Combination systems exhibits dual functions like oximetry and detection in cellular and molecular imaging [29].
5.4.1.2 Therapeutic component
The therapeutic component includes drug molecule that is associated with diagnostic component or carrier system. Examples of the former are radiotracer-labeled non-peptide like gallium-68-labeled bisphosphonates for osteoblastic bone metastases and peptide-based molecules such as gallium-68-labeled somatostatin analogs for somatostatin receptor which targets neuroendocrine tumors. Examples of therapeutic components associated with a carrier system are where integrated entities are attaches to macromolecular carrier covalently. In addition to this, drug molecules co-encapsulation is done with diagnostic components such as chelated radiotracers and gadolinium (III), quantum dots, gold nanoparticle into particulate carrier systems namely polymeric nanospheres, liposomes, polymersomes, and mesoporous silica nanoparticles.
5.5 The application of theranostics in cancer
Cancer is a serious condition of heterogeneous group of diseases where there is uncontrolled and rapid cell growth. This is because of changes at genetic and/or epigenetic level in patient’s body. Current treatment for cancer is chemotherapy, radiotherapy, immunotherapy and surgery.
Chemotherapy is not that much useful as a very low level of concentration of drug reaches the tumor. Moreover there is chances development of resistance during treatment and associated side effects. For example, chemotherapeutic agents known as taxanes have emerged as one of the most powerful classes of compounds to combat cancer, exhibiting a wide range of activity. The tubulin/microtubule complex has been proven to be a clinically useful antitumor target. The examples of chemotherapeutics that act via perturbation of tubulin polymerization include paclitaxel (Taxol®), docetaxel (Taxotere®), vinblastine, and discodermolide. First, docetaxel is a semi-synthetic derivative of paclitaxel. Next, vinblastine, unlike the other three compounds that all stabilize microtubules, aggregates tubulin and leads to microtubule depolymerisation. Randomized clinical trials evaluating docetaxel and paclitaxel in a first-line treatment setting for metastatic breast, lung, ovarian, and digestive cancers, as well as in the adjuvant setting for breast cancer, have confirmed that taxanes are leading contributors to the armamentarium of cancer treatments. Paclitaxel is used as a first-line chemotherapy treatment for NSCLC, but patients’ acquired resistance becomes a critical problem.
Here nanomedicine is better as it allows molecular targeting to get higher concentrations of drug molecules at targeted site. Studies have been to make sure that required amount of drug reaches the site actively or passively which ensures better therapeutic index.
Few examples of nanomedicine in this context are polymeric micelles, polymer-drug conjugates and liposomes. Whereas traditional small molecular drugs n get eliminated from bloodstream quickly but nanomedicine possess longer half-lives.
Furthermore there is enhanced bioavailability and augmented tumor delivery. In addition to it integration of imaging and nanomedicine helps as diagnostic arm of theranostics. The advantages of using such strategy are immense, that will assist in management of oncogenic conditions with the help of theranostics [30].
Applications of theranostics in medicine include:
It is a noninvasive molecular imaging method to evaluate of disease heterogeneity.
Gives better idea about biodistribution and about accumulation of drug at target-site.
Better understanding of process of local drug release.
Facilitation of drug release (through application of stimuli-responsive theranostics).
Prediction of drug responses and associated adverse effects with personalized therapies [31].
6. Health and safety
Radiopharmaceuticals are as safe as other medicine and before use they are tested carefully.
The quantity of the pharmaceutical part of the radiopharmaceutical is very small, generally 1/10th of a millionth of an ounce. The risk of a reaction is 2–3 incidents per 100,000 injections, over 50% of which are rashes as compared to 2000–3000 per 100,000 injections of X-ray contrast media.
For childrens most radiopharmaceuticals, the amount of radiation used for a diagnostic test is very low and considered safe [32].
Radiopharmaceuticals usually are not recommended for use during pregnancy. This is to avoid exposing the fetus to radiation. His is specially important with radiopharmaceuticals that contain radioactive iodine, which can go to the baby’s thyroid gland and in high enough amounts may cause thyroid damage.
Although exposure to the radioactivity in very large doses can be harmful the radioactivity in radiopharmaceuticals is carefully selected by the nuclear medicine physician to be safe.
If anybody will be receiving albumin in the form of radioiodinated albumin, technetium Tc 99m albumin aggregated, technetium Tc 99m albumin colloid, or technetium Tc 99m albumin for test, Consult doctor if have ever had any unusual or allergic reaction to products containing human serum albumin [33].
Side effects: when radiopharmaceuticals are used in very small doses to study an organ of the body, side effects are rare and usually involve an allergic reaction. These effects may occur almost immediately or a few minutes after the radiopharmaceutical is given.
7. Conclusion
In recent past radiopharmaceuticals made steady progress towards nuclear imaging and therapy. The benefit of molecular imaging and therapy can obtain when required amount of diagnostic probes reaches the targeted site. Effort have been taken in enhancing specificity of targeted radiotracers in both pre-clinical research and clinical trials. In recent discussions the advancement in the said field has been discussed taking into account multi-modal molecular imaging probes for sentinel lymph node mapping and image-guided surgery, radiotracers for targeted imaging of cancer and neurodegenerative diseases, along with probes for monitoring therapy responses. For better diagnosis and therapy design of radiopharmaceuticals as well as route of administration plays a major role. At last dose of radioactive medicine should be set with caution to prevent over exposure of patient, the principle of ‘As Low as Reasonably Achievable’ (ALARA) used for protection of employee as well as general public. The knowledge about medical physics is essential because of interactions between ionizing radiation and biological tissues. According to author we can be optimistic for the future growth of radiopharmaceuticals. This trend can be seen in recent future with the help of thriving research and fast translations into clinic. The high cost, demanding hardware requirements and specialized personnel training are major factors that may confine the development of radiopharmaceuticals. However, the huge needs for nuclear medicine from the public and the benefits to patient care far outweigh the risks.
\n',keywords:"radionuclides, nuclear medicines, nuclear imaging, theranostics, radiopharmaceuticals",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71624.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71624.xml",downloadPdfUrl:"/chapter/pdf-download/71624",previewPdfUrl:"/chapter/pdf-preview/71624",totalDownloads:1040,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:3,totalAltmetricsMentions:4,impactScore:1,impactScorePercentile:70,impactScoreQuartile:3,hasAltmetrics:1,dateSubmitted:"May 22nd 2019",dateReviewed:"February 23rd 2020",datePrePublished:"April 24th 2020",datePublished:"January 7th 2021",dateFinished:"March 31st 2020",readingETA:"0",abstract:"Malignancy and many inflammatory diseases have become a major concern for mankind over the years. The conventional therapy of these diseases lacks the effectiveness of the better diagnosis and targeted treatment of these diseases, but nuclear medicine can be regarded as a savior in the current scenario. Over the years, radioactivity of radioisotopes has been employed for treatment of many diseases. Nuclear medicines came up with radiopharmaceuticals that impart the ability to destroy specific diseased cells with high-energy-emitting radionuclides. Moreover, the emergence of theranostics, which is a combination of single drug used both for diagnostic as well as therapeutic purpose, has added a new feather in the field of nuclear medicines for providing a specific and personalized treatment to the patient. The current chapter discusses about techniques used for imaging of these radionuclides for better therapy and diagnosis of the root cause of the concerned disease by positron emission tomography (PET)/CT and single photon emission computed tomography (SPECT)/CT as well as the advantages and disadvantages associated with them. It also describes about applications of theranostics and nuclear imaging in cancer treatment and their future perspective.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71624",risUrl:"/chapter/ris/71624",book:{id:"7769",slug:"medical-isotopes"},signatures:"Chanchal Deep Kaur, Koushlesh Kumar Mishra, Anil Sahu, Rajnikant Panik, Pankaj Kashyap, Saraswati Prasad Mishra and Anand Kumar",authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",fullName:"Anil Kumar Sahu",slug:"anil-kumar-sahu",email:"anil2484@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",institution:{name:"Chhattisgarh Swami Vivekanand Technical University",institutionURL:null,country:{name:"India"}}},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",fullName:"Koushlesh Mishra",slug:"koushlesh-mishra",email:"koushleshmishra@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",fullName:"Sarawati Prasad Mishra",slug:"sarawati-prasad-mishra",email:"saraswatim3@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",fullName:"Chanchal Deep Kaur",slug:"chanchal-deep-kaur",email:"dr.chanchaldeep@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction to radioisotopes and radiopharmaceuticals",level:"1"},{id:"sec_1_2",title:"1.1 Radiopharmaceuticals",level:"2"},{id:"sec_2_2",title:"1.2 Technetium 99m",level:"2"},{id:"sec_2_3",title:"1.2.1 Bone",level:"3"},{id:"sec_3_3",title:"1.2.2 Kidney",level:"3"},{id:"sec_4_3",title:"1.2.3 Brain",level:"3"},{id:"sec_5_3",title:"1.2.4 Heart",level:"3"},{id:"sec_6_3",title:"1.2.5 Lungs",level:"3"},{id:"sec_8_2",title:"1.3 Adverse reactions",level:"2"},{id:"sec_10",title:"2. Recent approaches of injectable radiopharmaceuticals as nuclear medicine for imaging and therapy",level:"1"},{id:"sec_10_2",title:"2.1 SPECT and scintigraphy",level:"2"},{id:"sec_10_3",title:"2.1.1 Current status",level:"3"},{id:"sec_12_2",title:"2.2 PET",level:"2"},{id:"sec_12_3",title:"2.2.1 Current status",level:"3"},{id:"sec_13_3",title:"2.2.2 Advances",level:"3"},{id:"sec_15_2",title:"2.3 PET/MRI",level:"2"},{id:"sec_16_2",title:"2.4 Future perspectives",level:"2"},{id:"sec_16_3",title:"2.4.1 Simultaneous X-ray and nuclear imaging",level:"3"},{id:"sec_19",title:"3. Different types and applications of radioisotopes for imaging and therapy",level:"1"},{id:"sec_19_2",title:"3.1 Applications",level:"2"},{id:"sec_21",title:"4. Advantages and disadvantages of injectable radiopharmaceuticals",level:"1"},{id:"sec_21_2",title:"4.1 Properties of all radiopharmaceutical injectable",level:"2"},{id:"sec_21_3",title:"4.1.1 Advantages",level:"3"},{id:"sec_22_3",title:"4.1.2 Disadvantages",level:"3"},{id:"sec_25",title:"5. Theranostics",level:"1"},{id:"sec_25_2",title:"5.1 Theranostics: Nuclear Medicine Imaging",level:"2"},{id:"sec_26_2",title:"5.2 Therapeutic bullets",level:"2"},{id:"sec_27_2",title:"5.3 Nuclear Medicine Imaging",level:"2"},{id:"sec_28_2",title:"5.4 Theranostics: Zevalin therapy",level:"2"},{id:"sec_28_3",title:"5.4.1 Characteristics",level:"3"},{id:"sec_28_4",title:"5.4.1.1 Diagnostic component",level:"4"},{id:"sec_29_4",title:"5.4.1.2 Therapeutic component",level:"4"},{id:"sec_32_2",title:"5.5 The application of theranostics in cancer",level:"2"},{id:"sec_34",title:"6. Health and safety",level:"1"},{id:"sec_35",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'The Medicines Act 1968 (Application to Radiopharmaceutical-associated Products) Regulations. London: HMSO; 1992. Available from: www.legislation.gov.uk/uksi/1992/605/contents/made [Accessed: 03 June 2011]'},{id:"B2",body:'Theobald T. Sampson’s Textbook of Radiopharmacy. 4th ed. London: Pharmaceutical Press; 2011'},{id:"B3",body:'Administration of Radioactive Substances Advisory Committee. Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and Use of Sealed Radioactive Sources. 2006. Available from: www.arsac.org.uk/notes_for_guidance [Accessed: 03 June 2011]'},{id:"B4",body:'International Commission on Radiological Protection. Radiation dose to the patient from radiopharmaceuticals. Annals of the ICRP. 1988;18:1-4'},{id:"B5",body:'Chowdhury FU, Scarsbrook AF. The role of hybrid SPECT-CT in oncology: Current and emerging clinical applications. 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Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy. Current Pharmaceutical Design. 2014;20(32):5218-5244'},{id:"B29",body:'Ma X, Zhao Y, Liang X-J. Theranostic nanoparticles engineered for clinic and pharmaceutics. Accounts of Chemical Research. 2011;44:1114-1122'},{id:"B30",body:'Moghimi SM, Hunter AC, Murray JC. Nanomedicine: Current status and future prospects. The FASEB Journal. 2005;19:311-330'},{id:"B31",body:'Leeds NE. The clinical application of radiopharmaceuticals. Drugs. 1990;40(5):713-721'},{id:"B32",body:'Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chemical Reviews. 1999;99:2269-2292'},{id:"B33",body:'Ercan MT, Caglar M. Therapeutic radiopharmaceuticals. Current Pharmaceutical Design. 2000;6:1085-1121'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Chanchal Deep Kaur",address:"chanchaldeep@gmail.com",affiliation:'
Shri Rawatpura Sarkar Institute of Pharmacy, India
Sant Gahira Guru Vishwavidyalaya, Sarguja Ambikapur, India
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1. Introduction to radioisotopes and radiopharmaceuticals
Scientist has discovered that earth contains many elements with varying configuration. These elements with varying configuration are called isotopes. Isotopes are atoms with same atomic number with varying atomic weight. Isotopes can be divided into two parts depending on the ability to emit radiation. One that does not emit radiations is called stable isotopes and other are called unstable isotopes. Unstable isotopes emit radiations to achieve a more stable configuration. These are called as radioisotopes. Instability of radioisotopes is due to presence of unstable combination of neutron and proton in their atoms and nucleus contains excess of energy. This characteristic of radioisotopes can be natural or instability can be created artificially by changing the atoms. Naturally radioisotope is uranium-238 and it accounts to 0.7% of total naturally occurring isotopes. Artificial radioisotopes are fluorine and molybdenum which are produced artificially by using cyclotrons and nuclear reactors respectively. Presently there are around 3800 radioisotopes out of which 200 radioisotopes are being used. Among the isotopes that are used most of them are of artificial origin. Artificial radioisotopes are primarily made by two methods as mentioned above i.e. through nuclear reactor and by cyclotron. By nuclear reactor neutrons are introduced into the nucleus of atom whereas in case of cyclotron proton are introduced. To become stable radioisotopes emits alpha or beta particle along with electromagnetic radiation of gamma rays. This phenomenon is called as radioactive decay. These radioisotopes have variety of uses, when they are used in the field of pharmaceuticals they are termed as radiopharmaceuticals.
1.1 Radiopharmaceuticals
These are radioactive medicines that can be given by oral, intravenous or interstitial route to treat or diagnose malignancy. Administration of these drugs is done in the presence of specialist called radio pharmacist. These radioactive medicines have the ability to destroy cancerous cell by emitting radiation when it reaches its target cell. Radiopharmaceuticals for treatment and diagnosis of cancers associated with thyroid, brain, bones or lymphoma already been discovered.
In addition to treatment radiopharmaceuticals are also used for the purpose of diagnosis. The drugs used for diagnosis are called as tracers. The radiation of diagnostic radiopharmaceuticals is smaller as compared to radiation emitted by radiopharmaceuticals used for treatment. Radiopharmaceuticals are either single isotopes or sometimes the isotopes are combined with a kit [1]. The kit is prepackaging of ingredients which are sterile and are meant for preparation of radiopharmaceuticals. They are combination of substances such as antioxidant, buffer, reductant and ligands that are when combined with the radioisotopes produces the resultant product. Kits are very beneficial as they are not in contact with the outer environment so there is no chance of any contamination [2].
1.2 Technetium 99m
The isotope that is used for the purpose of labeling of kits used for diagnosis is technetium 99m abbreviated as 99mTc (Figure 1). It radiates only gamma radiation that is compatible with gamma camera. 99mTc also has the property of binding with the tracers. Advantage of technetium is that it has smaller biological half-life and better renal clearance for the unabsorbed radiopharmaceuticals that helps in getting a better quality of image from the absorbed ones. The dose of technetium depends on the kit, the organ on which it has to be used for imaging and on the test to be performed [3]. Determination of dose for children is very crucial as the cells are in dividing states so sensitivity towards radiation can be higher, organ size body ratio also varies to greater extent in comparison with adult. So in case of children a balanced level of administration is required [4].
Figure 1.
Chemical structure of technetium 99m.
Different kit labeled with 99mTc used for imaging of different organs is mentioned below.
1.2.1 Bone
For detection of the areas that are metabolizing the bones kits with bisphosphonates are used. Scan of bone is done by injecting radiopharmaceuticals into the peripheral vein of patient and then after 3 h imaging is done so that within the three hours the bisphosphonates will get incorporated into the osteoblast cells.
1.2.2 Kidney
For the imaging of kidney, there are three radiopharmaceuticals, namely
Mag-3; mertiatide is used for the purpose of determining the blood flow to the kidney and for graphically presenting the renal function. Mag-3 has a clearance of 94% after 3 h that helps in getting better quality of image and the exposure of patient to the radiation is also lower. DTPA; pentetate is used to determining rate of glomerular filtration during chemotherapy of kidney. Lastly DMSA; succimer is used a tool for studying morphology of renal cortex and ectopic kidney.
1.2.3 Brain
Kit used for the check the blood flow within the brain after conditions like epilepsy, migraine or Alzheimer’s disease or stroke of brain contains 99mTc-labeled exametazime. This is product of lipophilic origin without any charge on it and it penetrates better through blood brain barrier. It takes around one minute after injection for it to reach brain and up to 7% reaches the brain.
1.2.4 Heart
For cardiac imaging, two 99mTc-labeled are tetrofosmin and sestamibi which are employed to ascertain the degree to which myocardial infarction is severe and also help to point out the regions of cardiac ischemia. Images are collected at the state of rest and after stressed activity of cardiac cells. This injection are administered when patient must have consumed any kind of fatty meal. This helps in hepatobiliary clearance of administered radiopharmaceuticals thus aid in getting better image. But it should not be administered when patients has consumed some drugs such as nitrates or calcium channel blockers.
1.2.5 Lungs
In case of lungs scan it is used for the purpose of diagnosis of any kind of embolism in pulmonary tract. Lung scan be of two types perfusion scan or ventilation scan. First, one 99mTc-labeled macroaggregated albumin is injected in the peripheral vein, which is then carried to the pulmonary artery system. It does not get absorbed rather it gets distributed evenly in the capillary bed and helps in diagnosis. Where blood flow is good there will be larger number of particles giving out radiation, whereas where there will less perfusion then less particles will be seen.
In case of ventilation scan, patient is made to inhale radioactive substance such as krypton or 99mTc-labeled DTPA aerosol. Image is obtained where air is seen circulating in lungs [5].
1.3 Adverse reactions
The most common adverse reaction associated with radiopharmaceuticals is sweating, nausea, dry mouth and rashes.
2. Recent approaches of injectable radiopharmaceuticals as nuclear medicine for imaging and therapy
The aim of this chapter is to explain about advancements the injectable of biomaterials or radiopharmaceuticals origin used in molecular imaging, therapy and clinical diagnosis. On the basis of intrinsic radiation form, radioisotopes can be divided into following type namely gamma (γ) ray emitters, beta (positron β+ or electron β−) particles emitters and alpha (α) particles emitters or their combinations. In clinical practice and pre-clinical animal studies, mostly used radionuclides are gamma ray emitters like Technetium-99m (99mTc), Iodine-123 (123I) and Galium-67 (67Ga), Positron-emitting radionuclides namely Fluorine-18 (18F), Oxygen-15 (15O), Carbon-11 (11C) and Zirconium 89 (89Zr). Some β-emitters are Rhenium-186/Rhenium-188 (186Re/188Re), Strontium-89 (89Sr), and Yttrium-90 (90Y). Examples of therapeutic α-emitters are Actinium-225 (225Ac), Bismuth-213 (213Bi) and Astatine-211 (211At) [6]. The injected radiopharmaceuticals can be in simple ionic form or in carrier complex form. Carrier complex has better targeting ability for certain tissues and cells and pathways of disease. These are some radioisotopes used for imaging are as follows (Table 1):
In case of imaging, the major focus was development of 11C, 18F or 68Ga radiopharmaceuticals to be used in positron emission tomography (PET) and 99mTc-labeled agents for the used in single-photon emission computed tomography (SPECT) [8]. The merits associated with nuclear medicine are many such as it is noninvasive, it gives better in identifying exact region of tumor and beneficial for diagnosis of challenging diseases [9, 10]. In addition to this there is better quantitative analysis which is achieved with a numerous tools available. For example standard uptake values (SUVs) are taken in PET and in case of SPECT it is compared in vivo distribution of the injected materials [11]. There are some common nuclides mentioned in Table 2 which are used in radiation therapy are:
This content focuses on the developments in field of imaging technology in relevance to imaging of radionuclide therapy.
2.1 SPECT and scintigraphy
This type of decay of radionuclides determines about the modality for imaging. Planar scintigraphy or SPECT is used for imaging of 177Lu, 90Y, and 131I-which are used for radionuclide therapy. These emit γ-photons (or bremsstrahlung photons), which can be imaged by a γ-camera.
2.1.1 Current status
SPECT/CT systems which are used nowadays are used for both planar and tomographic imaging. Planar imaging is for acquiring whole-body images in when there is limitation of time. SPECT is meant for acquiring 3-dimensional data of structures which would otherwise overlap on each another on planar images.
Quantitative analysis of SPECT images is determined by converting the acquired counts in terms of distribution of absorbed dose (in Gy), which is beneficial for planning and dosimetry of therapy involving radionuclide. In clinical practice scatter correction is also implemented and is generally performed employing the triple-energy window method [13]. Quality of image can be enhanced by using resolution recovery. It is performed by characterizing the shape of the point-spread function accurately, that depends its distance from the camera and there is rotational variation due to the hexagonal pattern of the collimator septa. Reconstruction algorithm can be incorporated with point-spread function model subsequently [14].
Effects like scatter, blurring and attenuation which degrades image can be corrected to some extent, Although SPECT images can be degraded by partial-volume effects and quantification errors.
2.2 PET
18F-FDG PET is used for many PET studies that are in the field of clinical practice and is employed for staging and follow-up post radionuclide therapy. However, PET has application in planning of treatment, dosimetry, and assessment of treatment after radionuclide therapies.
2.2.1 Current status
Similar to SPECT quantitative PET is also used for correction techniques. Correction of attenuation for PET can be done through determination of the sonogram associated with attenuation correction, which works on the basis of co-registered CT data. Scatter correction is often done with single-scatter simulation method in clinical practice [15]. Correction for random counts is often done using delayed-event subtraction [16].
The difference in time between annihilation photons gives information regarding location of the annihilation and also about the line of response. Now time-of-flight information in the reconstruction at the time of back projection step enhances image quality. The availability of time-of-flight estimation has opened the opportunities for low positron abundance imaging isotopes like 90Y.
As intrinsic resolution of PET detectors are not freely available, so shape of the point-spread function is used to improve the quality of images by incorporating it during reconstruction method. This is called as resolution recovery.
When there are high count rate radiation detection systems does not work properly due to dead-time effect caused by pulse pile-up. Because of these Dead-time losses are corrected regularly.
2.2.2 Advances
There are better quality of PET images with enhanced resolutions and sensitivity due to regular improvement in the instrument which provides precise determination of the SUV [17].
2.3 PET/MRI
The advantages of PET/MRI over PET/CT are higher soft-tissue contrast that is essential for planning of treatment, dosimetry, and assessment post radionuclide therapies. Additionally, for accurate dosimetry it is beneficial as it provides the simultaneous coregisteration of MR images. Also, MRI can be employed for determining the tolerable dose with least organ damaging activity of radionuclide. Along with it anatomic and molecular images acquisition provides better motion correction.
Integrating of PET and MRI modalities is challenging as there will be interference between both the modalities. For instance, photomultiplier tubes that are present in PET detectors malfunction in magnetic fields exerted by MRI. In addition to this, PET module affects the radiofrequency signal associated with MRI [18]. Due to this, the first generation of PET/MRI systems modalities were separated. Integration of PET detectors and MR scanner has been done to obtain PET and MR images simultaneously. Detector systems is avalanche photodiodes types or SiPMs types which are not sensitive to magnetic field. The simultaneous measurement provides better 4-dimensional acquisitions because of spatial agreement of PET and MRI data.
Disadvantages associated with PET/MRI are high costs and the ferromagnetic metallic implants which are used is contradictory to MRI. In addition to this it’s challenging to correct attenuation of PET/MRI. For dosimetry it is essential to have accurate attenuation correction. As CT images are electron-density images and MR images are proton density image, CT image are better suited for attenuation correction. But MR images can be used for attenuation correction by using techniques such as segmentation-based or template- or atlas-based which derives electron density information from MR images [19]. Alternatively, estimation of the attenuation maps can be done by employing algorithms which uses the time-of-flight emission or transmission data [20].
2.4 Future perspectives
2.4.1 Simultaneous X-ray and nuclear imaging
Till today there are no real-time hybrid imaging modalities that can merge nuclear and anatomic for interventional purposes. Fluoroscopic imaging in combination with real-time nuclear imaging gives physicians with valuable information during procedures like as 90Y liver radio embolization by image distribution of the radionuclide in association with the anatomy and the interventional instruments that enhances therapeutic efficiency. Image of same field can be seen by arranging X-ray tube, an X-ray detector, and a γ-camera in a single line [21].
3. Different types and applications of radioisotopes for imaging and therapy
S. no
Radioisotopes
Uses
1.
Calcium-47
Important aid to biomedical researchers studying cellular functions and bone formation in mammals
2.
Caesuim-137
Used to treat cancerous tumors and to measure correct dosages of radioactive pharmaceuticals
3.
Chromium-51
Used in research in red blood cells survival studies
4.
Cobalt-57
Used as a tracer to diagnose pernicious anemia
5.
Cobalt-60
Used to sterilize surgical instruments and used in cancer treatment, food irradiation and radiography
6.
Copper-67
When injected to monoclonal antibodies into a cancer patient, helps the antibodies bind to and destroy the tumor
7.
Gallium-67
Used in medical diagnosis
8.
Iodine-123
Widely used to diagnose thyroid disorders and other metabolic disorders including brain functions
9.
Iodine-125
Major diagnostic tool used in clinical test and to diagnose thyroid disorders. Also used in biomedical research
10.
Iodine-129
Used to check some radioactivity counters in in-vitro diagnostic testing laboratories
11.
Iodine-131
Used to treat thyroid disorders (Graves’ disease)
12.
Iridium-192
In brachytherapy/tumor irradiation
13.
Phosphorous-32 and Phosphorous-33
Used in molecular biology and genetics research
14.
Technetium-99m
Most widely used radioactive pharmaceutical for diagnostic studies in nuclear medicine. Different chemical forms are used for brain, bone, liver, spleen and kidney imaging
15.
Uranium-234
Used in dental fixtures like crowns and dentures to provide a natural color and brightness
16.
Xenon-133
Used in nuclear medicine for lung ventilation and blood flow studies
3.1 Applications
Applications of different radioactive isotopes in nuclear medicine are [22]:
Cobalt-60 is used in radiation therapy for prevention of cancer.
Iodine-131 has been used for locating brain tumors, monitor activity of cardiac, liver and thyroid cells.
Carbon-14 used for determining metabolic changes happening in patients of diabetes, gout and anemia.
Carbon-11 is used to monitor organs during PET scan by tagging it into glucose.
Thallium-201 has been in use for determining damage in heart tissue, detection of tumors.
Technetium-99m act as radiotracer in medical diagnostics for obtaining the image of organs and study of blood flow. It also crucial for locating brain tumors and damaged heart cells [23].
4. Advantages and disadvantages of injectable radiopharmaceuticals
4.1 Properties of all radiopharmaceutical injectable
It should be sterile and free from Pyrogens. Sterility means absence of any living things even the spores or any related substances that can develop into something living. Culturing samples with special growth media is most common way to perform the assessment of sterility. Pyrogens are endotoxins that have the ability to cause pyrexia. They cannot be destroyed by autoclave and cannot be filtered. Testing for Pyrogens can be tested by using the rabbit test or the Limulus amebocyte lysate (LAL) test.
The isotonicity of injectable drug should be equal to 0.9% NaCl solution, and the pH should be 7.5.
In case of radioactive substance dose calibration should be done and it should be within ±10% of the prescribed dose. This calibration provides assurance that dose is as low as possible and it gives high quality image.
4.1.1 Advantages
It is used for diagnosis and treatment of patients.
It is commonly used to cure to cancers and can treat many other sites of disease.
Treats tumor such as bone metastasis.
Provide faster onset of relief from pain.
Single dose is effective for some patients.
Tests of nuclear medicine can be done on children.
Nuclear medicine procedure less costly and painless.
Nuclear medicine procedures are safe with no side effects [24].
4.1.2 Disadvantages
Some allergic reactions can be seen.
Risk of radiation is associated.
Myelosuppression may occur before chemotherapy.
Prolonged in convenience and discomfort can be experienced by patients due to administration of multiple fraction.
Nuclear medicine tests cannot use for pregnant women because of potential risk to unborn babies.
5. Theranostics
Theranostics is a combination of two words Therapeutics and diagnostics. This is an emerging field of medicine where drugs and/or techniques are used in combination for treatment as well as treatment. It’s a game changer as it provides diagnosis as well as therapy in single combination. It is economical as well as less time consuming. It uses PET scan to target tumor receptors which are present in tumor cell. If it is found in the cells radioactive drug is used to treat it. There are not much clinical trials found related to use of application of theranostics in prostate cancer by Australian Medicines Regulator—The Therapeutic Goods Administration (TGA) [25] (Figure 2).
Figure 2.
Theranostics working on tumor cell.
5.1 Theranostics: Nuclear Medicine Imaging
The Nuclear Medicine Imaging approach is revolutionized by use theranostics [targeted therapeutic (Rx) + companion diagnostic (DX)] to establish tools for specific molecular targeting. It provides personalized treatment plan for the patient by targeting specific targets. Various department of nuclear science can utilize theranostic agents [26].
5.2 Therapeutic bullets
Theranostics takes advantage of biological pathways specific to any system of human body to acquire diagnostic images. These images enhances the probability that the targeted therapeutic dosing of radiation that will only target disease part sparing the healthy one.
5.3 Nuclear Medicine Imaging
In past 100 years a similar kind of model for neuroendocrine tumors has been developed that has used radionuclide gallium-68. This PET radiotracer has been chelated to DOTA-octreotate and used for diagnosis of tumor with higher sensitivity compared to Indium-111 octreotide imaging.
The disease of patients can be determined by using the gallium-68 DOTA-TATE for targeting the somatostatin receptor volume and having image using hybrid scanner like PET-CT (Positron Emission Tomography-Computer Tomography). Lutetium Octreotate Therapy is a radiopharmaceuticals which emits beta radiation is available in 5 medical centers in north America and European medical centers [27].
Some of the milestones in the field of theranostics becoming personalized medicine are as follows:
Lutetium PSMA therapy for metastatic or treatment-resistant prostate cancer
Yttrium-90 SIRT therapy for liver cancer
Iodine-131 therapy for thyrotoxicosis and thyroid cancer
Radium-223 therapy for metastatic prostate cancer in bones
Yttrium-90 radiosynovectomy therapy for inflammatory synovitis of joints
Theranostics targeted therapy is difficult in case of cancer treatment due to heterogeneity of cancer cells. Ibritumomab a monoclonal antibody detects B-cells and produces the beta/alpha-emitting radiometal for destroying the lymphoma. SPECT imaging confirms distribution of antibody in the body. The indium-111 combined with radionuclide yttrium-90 transports beta particles for killing the B-cells [28] (Figure 3).
Figure 3.
Theranostics in cancer targeting and treatment.
5.4 Theranostics: Zevalin therapy
Zevalin therapy is used for determining the indications for relapsed or refractory, low-grade or follicular, B-cell non-Hodgkin’s lymphoma. Zevalin is FDA approved for the treatment of relapsed or refractory low-grade follicular. In the year 2008 Zevalin was approved as the first-line drug for follicular lymphoma in the European Union.
5.4.1 Characteristics
5.4.1.1 Diagnostic component
The diagnostic component contains radiotracer, a contrast agent molecule, and a particulate system with either inherent physical property like optical, magnetic property or an acquired physical property such as, contrast enhanced ultrasound property or combinations of both. Combination systems exhibits dual functions like oximetry and detection in cellular and molecular imaging [29].
5.4.1.2 Therapeutic component
The therapeutic component includes drug molecule that is associated with diagnostic component or carrier system. Examples of the former are radiotracer-labeled non-peptide like gallium-68-labeled bisphosphonates for osteoblastic bone metastases and peptide-based molecules such as gallium-68-labeled somatostatin analogs for somatostatin receptor which targets neuroendocrine tumors. Examples of therapeutic components associated with a carrier system are where integrated entities are attaches to macromolecular carrier covalently. In addition to this, drug molecules co-encapsulation is done with diagnostic components such as chelated radiotracers and gadolinium (III), quantum dots, gold nanoparticle into particulate carrier systems namely polymeric nanospheres, liposomes, polymersomes, and mesoporous silica nanoparticles.
5.5 The application of theranostics in cancer
Cancer is a serious condition of heterogeneous group of diseases where there is uncontrolled and rapid cell growth. This is because of changes at genetic and/or epigenetic level in patient’s body. Current treatment for cancer is chemotherapy, radiotherapy, immunotherapy and surgery.
Chemotherapy is not that much useful as a very low level of concentration of drug reaches the tumor. Moreover there is chances development of resistance during treatment and associated side effects. For example, chemotherapeutic agents known as taxanes have emerged as one of the most powerful classes of compounds to combat cancer, exhibiting a wide range of activity. The tubulin/microtubule complex has been proven to be a clinically useful antitumor target. The examples of chemotherapeutics that act via perturbation of tubulin polymerization include paclitaxel (Taxol®), docetaxel (Taxotere®), vinblastine, and discodermolide. First, docetaxel is a semi-synthetic derivative of paclitaxel. Next, vinblastine, unlike the other three compounds that all stabilize microtubules, aggregates tubulin and leads to microtubule depolymerisation. Randomized clinical trials evaluating docetaxel and paclitaxel in a first-line treatment setting for metastatic breast, lung, ovarian, and digestive cancers, as well as in the adjuvant setting for breast cancer, have confirmed that taxanes are leading contributors to the armamentarium of cancer treatments. Paclitaxel is used as a first-line chemotherapy treatment for NSCLC, but patients’ acquired resistance becomes a critical problem.
Here nanomedicine is better as it allows molecular targeting to get higher concentrations of drug molecules at targeted site. Studies have been to make sure that required amount of drug reaches the site actively or passively which ensures better therapeutic index.
Few examples of nanomedicine in this context are polymeric micelles, polymer-drug conjugates and liposomes. Whereas traditional small molecular drugs n get eliminated from bloodstream quickly but nanomedicine possess longer half-lives.
Furthermore there is enhanced bioavailability and augmented tumor delivery. In addition to it integration of imaging and nanomedicine helps as diagnostic arm of theranostics. The advantages of using such strategy are immense, that will assist in management of oncogenic conditions with the help of theranostics [30].
Applications of theranostics in medicine include:
It is a noninvasive molecular imaging method to evaluate of disease heterogeneity.
Gives better idea about biodistribution and about accumulation of drug at target-site.
Better understanding of process of local drug release.
Facilitation of drug release (through application of stimuli-responsive theranostics).
Prediction of drug responses and associated adverse effects with personalized therapies [31].
6. Health and safety
Radiopharmaceuticals are as safe as other medicine and before use they are tested carefully.
The quantity of the pharmaceutical part of the radiopharmaceutical is very small, generally 1/10th of a millionth of an ounce. The risk of a reaction is 2–3 incidents per 100,000 injections, over 50% of which are rashes as compared to 2000–3000 per 100,000 injections of X-ray contrast media.
For childrens most radiopharmaceuticals, the amount of radiation used for a diagnostic test is very low and considered safe [32].
Radiopharmaceuticals usually are not recommended for use during pregnancy. This is to avoid exposing the fetus to radiation. His is specially important with radiopharmaceuticals that contain radioactive iodine, which can go to the baby’s thyroid gland and in high enough amounts may cause thyroid damage.
Although exposure to the radioactivity in very large doses can be harmful the radioactivity in radiopharmaceuticals is carefully selected by the nuclear medicine physician to be safe.
If anybody will be receiving albumin in the form of radioiodinated albumin, technetium Tc 99m albumin aggregated, technetium Tc 99m albumin colloid, or technetium Tc 99m albumin for test, Consult doctor if have ever had any unusual or allergic reaction to products containing human serum albumin [33].
Side effects: when radiopharmaceuticals are used in very small doses to study an organ of the body, side effects are rare and usually involve an allergic reaction. These effects may occur almost immediately or a few minutes after the radiopharmaceutical is given.
7. Conclusion
In recent past radiopharmaceuticals made steady progress towards nuclear imaging and therapy. The benefit of molecular imaging and therapy can obtain when required amount of diagnostic probes reaches the targeted site. Effort have been taken in enhancing specificity of targeted radiotracers in both pre-clinical research and clinical trials. In recent discussions the advancement in the said field has been discussed taking into account multi-modal molecular imaging probes for sentinel lymph node mapping and image-guided surgery, radiotracers for targeted imaging of cancer and neurodegenerative diseases, along with probes for monitoring therapy responses. For better diagnosis and therapy design of radiopharmaceuticals as well as route of administration plays a major role. At last dose of radioactive medicine should be set with caution to prevent over exposure of patient, the principle of ‘As Low as Reasonably Achievable’ (ALARA) used for protection of employee as well as general public. The knowledge about medical physics is essential because of interactions between ionizing radiation and biological tissues. According to author we can be optimistic for the future growth of radiopharmaceuticals. This trend can be seen in recent future with the help of thriving research and fast translations into clinic. The high cost, demanding hardware requirements and specialized personnel training are major factors that may confine the development of radiopharmaceuticals. However, the huge needs for nuclear medicine from the public and the benefits to patient care far outweigh the risks.
\n',keywords:"radionuclides, nuclear medicines, nuclear imaging, theranostics, radiopharmaceuticals",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/71624.pdf",chapterXML:"https://mts.intechopen.com/source/xml/71624.xml",downloadPdfUrl:"/chapter/pdf-download/71624",previewPdfUrl:"/chapter/pdf-preview/71624",totalDownloads:1040,totalViews:0,totalCrossrefCites:1,dateSubmitted:"May 22nd 2019",dateReviewed:"February 23rd 2020",datePrePublished:"April 24th 2020",datePublished:"January 7th 2021",dateFinished:"March 31st 2020",readingETA:"0",abstract:"Malignancy and many inflammatory diseases have become a major concern for mankind over the years. The conventional therapy of these diseases lacks the effectiveness of the better diagnosis and targeted treatment of these diseases, but nuclear medicine can be regarded as a savior in the current scenario. Over the years, radioactivity of radioisotopes has been employed for treatment of many diseases. Nuclear medicines came up with radiopharmaceuticals that impart the ability to destroy specific diseased cells with high-energy-emitting radionuclides. Moreover, the emergence of theranostics, which is a combination of single drug used both for diagnostic as well as therapeutic purpose, has added a new feather in the field of nuclear medicines for providing a specific and personalized treatment to the patient. The current chapter discusses about techniques used for imaging of these radionuclides for better therapy and diagnosis of the root cause of the concerned disease by positron emission tomography (PET)/CT and single photon emission computed tomography (SPECT)/CT as well as the advantages and disadvantages associated with them. It also describes about applications of theranostics and nuclear imaging in cancer treatment and their future perspective.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/71624",risUrl:"/chapter/ris/71624",signatures:"Chanchal Deep Kaur, Koushlesh Kumar Mishra, Anil Sahu, Rajnikant Panik, Pankaj Kashyap, Saraswati Prasad Mishra and Anand Kumar",book:{id:"7769",type:"book",title:"Medical Isotopes",subtitle:null,fullTitle:"Medical Isotopes",slug:"medical-isotopes",publishedDate:"January 7th 2021",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-628-6",printIsbn:"978-1-83880-627-9",pdfIsbn:"978-1-83880-629-3",isAvailableForWebshopOrdering:!0,editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",fullName:"Anil Kumar Sahu",slug:"anil-kumar-sahu",email:"anil2484@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",institution:{name:"Chhattisgarh Swami Vivekanand Technical University",institutionURL:null,country:{name:"India"}}},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",fullName:"Koushlesh Mishra",slug:"koushlesh-mishra",email:"koushleshmishra@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",fullName:"Sarawati Prasad Mishra",slug:"sarawati-prasad-mishra",email:"saraswatim3@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",fullName:"Chanchal Deep Kaur",slug:"chanchal-deep-kaur",email:"dr.chanchaldeep@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction to radioisotopes and radiopharmaceuticals",level:"1"},{id:"sec_1_2",title:"1.1 Radiopharmaceuticals",level:"2"},{id:"sec_2_2",title:"1.2 Technetium 99m",level:"2"},{id:"sec_2_3",title:"1.2.1 Bone",level:"3"},{id:"sec_3_3",title:"1.2.2 Kidney",level:"3"},{id:"sec_4_3",title:"1.2.3 Brain",level:"3"},{id:"sec_5_3",title:"1.2.4 Heart",level:"3"},{id:"sec_6_3",title:"1.2.5 Lungs",level:"3"},{id:"sec_8_2",title:"1.3 Adverse reactions",level:"2"},{id:"sec_10",title:"2. Recent approaches of injectable radiopharmaceuticals as nuclear medicine for imaging and therapy",level:"1"},{id:"sec_10_2",title:"2.1 SPECT and scintigraphy",level:"2"},{id:"sec_10_3",title:"2.1.1 Current status",level:"3"},{id:"sec_12_2",title:"2.2 PET",level:"2"},{id:"sec_12_3",title:"2.2.1 Current status",level:"3"},{id:"sec_13_3",title:"2.2.2 Advances",level:"3"},{id:"sec_15_2",title:"2.3 PET/MRI",level:"2"},{id:"sec_16_2",title:"2.4 Future perspectives",level:"2"},{id:"sec_16_3",title:"2.4.1 Simultaneous X-ray and nuclear imaging",level:"3"},{id:"sec_19",title:"3. Different types and applications of radioisotopes for imaging and therapy",level:"1"},{id:"sec_19_2",title:"3.1 Applications",level:"2"},{id:"sec_21",title:"4. Advantages and disadvantages of injectable radiopharmaceuticals",level:"1"},{id:"sec_21_2",title:"4.1 Properties of all radiopharmaceutical injectable",level:"2"},{id:"sec_21_3",title:"4.1.1 Advantages",level:"3"},{id:"sec_22_3",title:"4.1.2 Disadvantages",level:"3"},{id:"sec_25",title:"5. Theranostics",level:"1"},{id:"sec_25_2",title:"5.1 Theranostics: Nuclear Medicine Imaging",level:"2"},{id:"sec_26_2",title:"5.2 Therapeutic bullets",level:"2"},{id:"sec_27_2",title:"5.3 Nuclear Medicine Imaging",level:"2"},{id:"sec_28_2",title:"5.4 Theranostics: Zevalin therapy",level:"2"},{id:"sec_28_3",title:"5.4.1 Characteristics",level:"3"},{id:"sec_28_4",title:"5.4.1.1 Diagnostic component",level:"4"},{id:"sec_29_4",title:"5.4.1.2 Therapeutic component",level:"4"},{id:"sec_32_2",title:"5.5 The application of theranostics in cancer",level:"2"},{id:"sec_34",title:"6. Health and safety",level:"1"},{id:"sec_35",title:"7. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'The Medicines Act 1968 (Application to Radiopharmaceutical-associated Products) Regulations. London: HMSO; 1992. Available from: www.legislation.gov.uk/uksi/1992/605/contents/made [Accessed: 03 June 2011]'},{id:"B2",body:'Theobald T. Sampson’s Textbook of Radiopharmacy. 4th ed. London: Pharmaceutical Press; 2011'},{id:"B3",body:'Administration of Radioactive Substances Advisory Committee. Notes for Guidance on the Clinical Administration of Radiopharmaceuticals and Use of Sealed Radioactive Sources. 2006. Available from: www.arsac.org.uk/notes_for_guidance [Accessed: 03 June 2011]'},{id:"B4",body:'International Commission on Radiological Protection. Radiation dose to the patient from radiopharmaceuticals. Annals of the ICRP. 1988;18:1-4'},{id:"B5",body:'Chowdhury FU, Scarsbrook AF. The role of hybrid SPECT-CT in oncology: Current and emerging clinical applications. Clinical Radiology. 2008;63(3):241-251'},{id:"B6",body:'Hamoudeh M, Kamleh MA, Diab R, Fessi H. Advanced Drug Delivery Reviews. 2008;60(12):1329-1346'},{id:"B7",body:'Sugashwaran J. Radioactivity—Natural and Artificial Radioactive Isotopes—Properties and Clinical Uses. Bangalore: Department of Radiation Oncology; 2014'},{id:"B8",body:'Holland JP, Williamson MJ, Lewis JS. Molecular Imaging. 2010;9(1):1-20'},{id:"B9",body:'Hoh CK, Schiepers C, Seltzer MA, Gambhir SS, Silverman DHS, Czernin J, et al. Seminars in Nuclear Medicine. 1997;27(2):94-106'},{id:"B10",body:'Öberg K, Eriksson B. Best Practice & Research Clinical Endocrinology & Metabolism. 2005;19(2):265-276'},{id:"B11",body:'Kinahan PE, Fletcher JW. Seminars in Ultrasound, CT and MRI. 2010;31(6):496-505'},{id:"B12",body:'Sathekge M. Targeted radionuclide therapy has the potential to selectively deliver radiation to diseased cells with minimal toxicity to surrounding tissues. Continuing Medical Education. 2013;31(8)'},{id:"B13",body:'Ogawa K, Harata Y, Ichihara T, Kubo A, Hashimoto S. A practical method for position-dependent Compton-scatter correction in single photon emission CT. IEEE Transactions on Medical Imaging. 1991;10:408-412'},{id:"B14",body:'Zeng GL, Gullberg GT, Tsui BMW, Terry JA. Three-dimensional iterative reconstruction algorithms with attenuation and geometric point response correction. IEEE Transactions on Nuclear Science. 1991;38:693-702'},{id:"B15",body:'Zaidi H, Montandon M-L. Scatter compensation techniques in PET. PET Clinics. 2007;2:219-234'},{id:"B16",body:'Casey ME, Hoffman EJ. Quantitation in positron emission computed tomography: 7. A technique to reduce noise in accidental coincidence measurements and coincidence efficiency calibration. Journal of Computer Assisted Tomography. 1986;10:845-850'},{id:"B17",body:'Bockisch A, Freudenberg LS, Schmidt D, et al. Hybrid imaging by SPECT/CT and PET/CT: Proven outcomes in cancer imaging. Seminars in Nuclear Medicine. 2009;39(4):276-289'},{id:"B18",body:'Torigian DA, Zaidi H, Kwee TC, et al. PET/MR imaging: Technical aspects and potential clinical applications. Radiology. 2013;267:26-44'},{id:"B19",body:'Keereman V, Mollet P, Berker Y, Schulz V, Vandenberghe S. Challenges and current methods for attenuation correction in PET/MR. Magma. 2013;26:81-98'},{id:"B20",body:'Nuyts J, Dupont P, Stroobants S, Benninck R, Mortelmans L, Suetens P. Simultaneous maximum a posteriori reconstruction of attenuation and activity distributions from emission sinograms. IEEE Transactions on Medical Imaging. 1999;18:393-403'},{id:"B21",body:'Beijst C, Elschot M, Viergever MA, de Jong HWAM. Toward simultaneous real-time fluoroscopic and nuclear imaging in the intervention room. Radiology. 2016;278:232-238'},{id:"B22",body:'Cuaron JJ, Hirsch JA, Medich DC, et al. A proposed methodology to select radioisotopes for use in radionuclide therapy. AJNR. American Journal of Neuroradiology. 2009;30:1824-1829'},{id:"B23",body:'Bhattacharyya S, Dixit M. Metallic radionuclides in the development of diagnostic and therapeutic radiopharmaceuticals. Dalton Transactions. 2011;40(23):6112-6128'},{id:"B24",body:'McCready VR. Milestones in nuclear medicine. European Journal of Nuclear Medicine. 2000;27(Suppl):S49-S79'},{id:"B25",body:'Baum RP, Kulkarni HR. Theranostics: From molecular imaging using Ga-68 labeled tracers and PET/CT to personalized radionuclide therapy—The Bad Berka experience. Theranostics. 2012;2:437-447'},{id:"B26",body:'Janib SM, Moses AS, MacKay JA. Imaging and drug delivery using theranostic nanoparticles. Advanced Drug Delivery Reviews. 2010;62:1052-1063'},{id:"B27",body:'Jokerst JV, Gambhir SS. Molecular imaging with theranostic nanoparticles. Accounts of Chemical Research. 2011;44:1050-1060'},{id:"B28",body:'Aerts A, Impens NR, Gijs M, et al. Biological carrier molecules of radiopharmaceuticals for molecular cancer imaging and targeted cancer therapy. Current Pharmaceutical Design. 2014;20(32):5218-5244'},{id:"B29",body:'Ma X, Zhao Y, Liang X-J. Theranostic nanoparticles engineered for clinic and pharmaceutics. Accounts of Chemical Research. 2011;44:1114-1122'},{id:"B30",body:'Moghimi SM, Hunter AC, Murray JC. Nanomedicine: Current status and future prospects. The FASEB Journal. 2005;19:311-330'},{id:"B31",body:'Leeds NE. The clinical application of radiopharmaceuticals. Drugs. 1990;40(5):713-721'},{id:"B32",body:'Volkert WA, Hoffman TJ. Therapeutic radiopharmaceuticals. Chemical Reviews. 1999;99:2269-2292'},{id:"B33",body:'Ercan MT, Caglar M. Therapeutic radiopharmaceuticals. Current Pharmaceutical Design. 2000;6:1085-1121'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Chanchal Deep Kaur",address:"chanchaldeep@gmail.com",affiliation:'
Shri Rawatpura Sarkar Institute of Pharmacy, India
Sant Gahira Guru Vishwavidyalaya, Sarguja Ambikapur, India
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Therefore, it is necessary to evaluate the effectiveness of determining the age of deposition using zircon age data. We carried out U–Pb dating of detrital zircons from sandstone at eight sites in the Cretaceous Shimanto accretionary complex on Kii Peninsula, Japan, with the aim of evaluating the accuracy of U–Pb zircon ages as indicators of the depositional age of sedimentary rocks by comparing zircon ages with radiolarian ages. Our results reveal zircons of late Cretaceous age, and the youngest peak ages are in good agreement with depositional ages inferred from radiolarian fossils. In addition, the youngest peak ages become younger as tectono-structurally downwards, and this tendency is clearer for the zircon ages than for the radiolarian ages. These results indicate that newly crystalized zircons were continuously supplied to the sediment by constant igneous activity during the late Cretaceous and that zircon ages provide remarkably useful information for determining the age of deposition in the Cretaceous Shimanto accretionary complex.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Tetsuya Tokiwa, Makoto Takeuchi, Yusuke Shimura, Kazuho Shobu,\nAkari Ota, Koshi Yamamoto and Hiroshi Mori",authors:[{id:"150531",title:"Dr.",name:"Koshi",middleName:null,surname:"Yamamoto",slug:"koshi-yamamoto",fullName:"Koshi Yamamoto"},{id:"194144",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Tokiwa",slug:"tetsuya-tokiwa",fullName:"Tetsuya Tokiwa"},{id:"204259",title:"Dr.",name:"Makoto",middleName:null,surname:"Takeuchi",slug:"makoto-takeuchi",fullName:"Makoto Takeuchi"},{id:"204260",title:"Mr.",name:"Yusuke",middleName:null,surname:"Shimura",slug:"yusuke-shimura",fullName:"Yusuke Shimura"},{id:"204261",title:"Mr.",name:"Kazuho",middleName:null,surname:"Shobu",slug:"kazuho-shobu",fullName:"Kazuho Shobu"},{id:"204262",title:"Ms.",name:"Akari",middleName:null,surname:"Ota",slug:"akari-ota",fullName:"Akari Ota"},{id:"204263",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Mori",slug:"hiroshi-mori",fullName:"Hiroshi Mori"}]},{id:"55296",doi:"10.5772/68112",title:"Alteration Reaction and Mass Transfer via Fluids with Progress of Fracturing along the Median Tectonic Line, Mie Prefecture, Southwest Japan",slug:"alteration-reaction-and-mass-transfer-via-fluids-with-progress-of-fracturing-along-the-median-tecton",totalDownloads:1203,totalCrossrefCites:1,totalDimensionsCites:8,abstract:"We have analyzed mass transfer in the cataclasite samples collected from the Median Tectonic Line, southwest Japan, in which the degree of fracturing is well correlated with the bulk rock chemical compositions determined by the X-ray fluorescence (XRF) analysis. The results of “isocon” analysis indicate not only a large volume increase up to 110% but also the two-stage mass transfer during cataclasis. At the first stage from the very weakly to weakly fractured rocks, the weight percents of SiO2, Na2O, and K2O increase, while those of TiO2, FeO, MnO, MgO, and CaO decrease. At the second stage from the weakly to moderately and strongly fractured rocks, the trend of mass transfer is reversed. The principal component analysis reveals that the variation of chemical compositions in the cataclasite samples can be mostly interpreted by the mass transfer via fluids and by the difference in chemical composition in the protolith rocks to lesser degree. Finally, the changes in the modal composition of minerals with increasing cataclasis analyzed by the X-ray diffraction (XRD) with the aid of “RockJock” software clearly elucidate that the mass transfer of chemical elements was caused by dissolution and precipitation of minerals via fluids in the cataclasite samples.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yumi Kaneko, Toru Takeshita, Yuto Watanabe, Norio Shigematsu\nand Ko‐Ichiro Fujimoto",authors:[{id:"194157",title:"M.Sc.",name:"Yumi",middleName:null,surname:"Kaneko",slug:"yumi-kaneko",fullName:"Yumi Kaneko"},{id:"204607",title:"Prof.",name:"Toru",middleName:null,surname:"Takeshita",slug:"toru-takeshita",fullName:"Toru Takeshita"},{id:"204608",title:"MSc.",name:"Yuto",middleName:null,surname:"Watanabe",slug:"yuto-watanabe",fullName:"Yuto Watanabe"},{id:"204609",title:"Dr.",name:"Norio",middleName:null,surname:"Shigematsu",slug:"norio-shigematsu",fullName:"Norio Shigematsu"},{id:"204610",title:"Dr.",name:"Ko-Ichiro",middleName:null,surname:"Fujimoto",slug:"ko-ichiro-fujimoto",fullName:"Ko-Ichiro Fujimoto"}]},{id:"54870",doi:"10.5772/67559",title:"Deposition and Deformation of Modern Accretionary-Type Forearc Basins: Linking Basin Formation and Accretionary Wedge Growth",slug:"deposition-and-deformation-of-modern-accretionary-type-forearc-basins-linking-basin-formation-and-ac",totalDownloads:1765,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Since a comprehensive review of forearc basins was published by Dickinson more than 20 years ago, a significant amount of new data about them have been published. These recent studies revealed details of depositional and deformation styles in the forearc basins, suggesting the formation processes were not unique. In this chapter, we reviewed modern forearc basins to understand how is the basin stratigraphy related with growth of accretionary wedges. The results indicate forearc basin can be classified into two (single‐ and two‐wedge models) plus one (strike‐slip model): (1) the single‐wedge model which is characterized by landward tilting of the basin strata ascribed to asymmetrical doubly vergent (single‐vergent) uplift of the outer arc high with forethrusts (seaward‐vergent thrusts in the pro‐wedge); (2) the two‐wedge model which is marked by contractional deformation caused by symmetrical doubly vergent uplift of the wedge with forethrusts in the prowedge and back‐thrusts (landward‐vergent thrusts) in the retro‐wedge; and (3) the strike‐slip model which is an additional one being represented by transpressional and/or transtensional deformations due to oblique subduction. We speculate that these models spatially and temporally depend on material fluxes at the plate interfaces that affect geometry and mechanical strength of backstops.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Atsushi Noda and Ayumu Miyakawa",authors:[{id:"161716",title:"Dr.",name:"Atsushi",middleName:null,surname:"Noda",slug:"atsushi-noda",fullName:"Atsushi Noda"},{id:"204603",title:"Dr.",name:"Ayumu",middleName:null,surname:"Miyakawa",slug:"ayumu-miyakawa",fullName:"Ayumu Miyakawa"}]},{id:"54596",doi:"10.5772/67960",title:"Paleomagnetic Studies on Miocene Sequences of Hokutan and Tottori Groups in Southwest Japan: Implications for Middle Miocene Rotational Movement of Southwest Japan Block Associated with the Japan Sea Opening",slug:"paleomagnetic-studies-on-miocene-sequences-of-hokutan-and-tottori-groups-in-southwest-japan-implicat",totalDownloads:1511,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Miocene sequences composed of volcanic rocks and overlying marine sediments distributing at the Japan Sea side of Southwest Japan have been considered to form related to the rifting and subsequent spreading of the Japan Sea back-arc basin in Miocene time. We performed paleomagnetic investigations on the sequences in the eastern San’in district, the Hokutan and Tottori Groups. Paleomagnetic analyses on samples from 33 sites indicated that characteristic magnetic components from five sites of volcanic rocks in the Hokutan Group and from four sites of marine sediments in the Tottori Group were regarded as primary components. An obtained paleomagnetic direction of the volcanic rocks has an easterly deflected declination (D = 23.9° ± 20.2°), while that of the marine sediments shows no significant deflection in declination (D = 17.8° ± 19.1°). Through the comparison with paleomagnetic data from the Miocene sequences in Southwest Japan, it is suggested that magnetic polarities of the volcanic and sedimentary sequences are assigned to C5Cn and C5Br-C5Bn, respectively, and that the eastern San’in district suffered a clockwise rotation of 24° at around 16 Ma after the early Miocene volcanic activity and before the middle Miocene marine transgression in the whole clockwise rotation process of Southwest Japan related to the Japan Sea opening.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Naoto Ishikawa, Takashi Suzuki and Shiro Ishida",authors:[{id:"194180",title:"Dr.",name:"Naoto",middleName:null,surname:"Ishikawa",slug:"naoto-ishikawa",fullName:"Naoto Ishikawa"},{id:"204504",title:"Dr.",name:"Takashi",middleName:null,surname:"Suzuki",slug:"takashi-suzuki",fullName:"Takashi Suzuki"},{id:"204505",title:"Prof.",name:"Shiro",middleName:null,surname:"Ishida",slug:"shiro-ishida",fullName:"Shiro Ishida"}]},{id:"54492",doi:"10.5772/67434",title:"Three-Dimensional Architecture of the Median Tectonic Line in Southwest Japan Based on Detailed Reflection Seismic and Drilling Surveys",slug:"three-dimensional-architecture-of-the-median-tectonic-line-in-southwest-japan-based-on-detailed-refl",totalDownloads:1578,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"The subsurface morphology of an arc-bisecting tectonic zone has been unraveled by means of well-organized seismic investigation with the aid of borehole stratigraphic control. The Median Tectonic Line (MTL) active fault system in southwestern Japan, one of the world’s largest intraplate transcurrent faults, is driven by the recent oblique subduction of the Philippine Sea Plate. Six tied seismic profiles covering the mountainous range, the southern foothill of which is truncated by the MTL, were used to visualize the Quaternary basins on both feet of the Izumi Mountains. North- and east-trending basement deformation was confirmed on the northern and southern sides of the watershed, respectively; this deformation reflects the spatial diversity in tectonic stress. Seismic data on the southern Izumi flank revealed a low-angle fault parallel to the MTL active fault system; this fault may be interpreted as a dormant structure that developed from 6 to 2 Ma under the intermittent increases of the compressive regime. A kink zone in the upthrown block of the thrust was identified on seismic profiles and continuously traced through field geological survey. This zone confirms the prevailing contractional phase related to the transient convergence mode of the oceanic plate.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yasuto Itoh, Tomotaka Iwata and Keiji Takemura",authors:[{id:"46893",title:"Dr.",name:"Yasuto",middleName:null,surname:"Itoh",slug:"yasuto-itoh",fullName:"Yasuto Itoh"},{id:"167628",title:"Dr.",name:"Keiji",middleName:null,surname:"Takemura",slug:"keiji-takemura",fullName:"Keiji Takemura"},{id:"203882",title:"Prof.",name:"Tomotaka",middleName:null,surname:"Iwata",slug:"tomotaka-iwata",fullName:"Tomotaka Iwata"}]}],mostDownloadedChaptersLast30Days:[{id:"54840",title:"Effectiveness for Determination of Depositional Age by Detrital Zircon U–Pb Age in the Cretaceous Shimanto Accretionary Complex of Japan",slug:"effectiveness-for-determination-of-depositional-age-by-detrital-zircon-u-pb-age-in-the-cretaceous-sh",totalDownloads:1458,totalCrossrefCites:8,totalDimensionsCites:13,abstract:"Detrital zircon U–Pb ages indicate the crystallization age. Therefore, it is necessary to evaluate the effectiveness of determining the age of deposition using zircon age data. We carried out U–Pb dating of detrital zircons from sandstone at eight sites in the Cretaceous Shimanto accretionary complex on Kii Peninsula, Japan, with the aim of evaluating the accuracy of U–Pb zircon ages as indicators of the depositional age of sedimentary rocks by comparing zircon ages with radiolarian ages. Our results reveal zircons of late Cretaceous age, and the youngest peak ages are in good agreement with depositional ages inferred from radiolarian fossils. In addition, the youngest peak ages become younger as tectono-structurally downwards, and this tendency is clearer for the zircon ages than for the radiolarian ages. These results indicate that newly crystalized zircons were continuously supplied to the sediment by constant igneous activity during the late Cretaceous and that zircon ages provide remarkably useful information for determining the age of deposition in the Cretaceous Shimanto accretionary complex.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Tetsuya Tokiwa, Makoto Takeuchi, Yusuke Shimura, Kazuho Shobu,\nAkari Ota, Koshi Yamamoto and Hiroshi Mori",authors:[{id:"150531",title:"Dr.",name:"Koshi",middleName:null,surname:"Yamamoto",slug:"koshi-yamamoto",fullName:"Koshi Yamamoto"},{id:"194144",title:"Dr.",name:"Tetsuya",middleName:null,surname:"Tokiwa",slug:"tetsuya-tokiwa",fullName:"Tetsuya Tokiwa"},{id:"204259",title:"Dr.",name:"Makoto",middleName:null,surname:"Takeuchi",slug:"makoto-takeuchi",fullName:"Makoto Takeuchi"},{id:"204260",title:"Mr.",name:"Yusuke",middleName:null,surname:"Shimura",slug:"yusuke-shimura",fullName:"Yusuke Shimura"},{id:"204261",title:"Mr.",name:"Kazuho",middleName:null,surname:"Shobu",slug:"kazuho-shobu",fullName:"Kazuho Shobu"},{id:"204262",title:"Ms.",name:"Akari",middleName:null,surname:"Ota",slug:"akari-ota",fullName:"Akari Ota"},{id:"204263",title:"Dr.",name:"Hiroshi",middleName:null,surname:"Mori",slug:"hiroshi-mori",fullName:"Hiroshi Mori"}]},{id:"54341",title:"Oki-Dozen Dike Swarm: Effect of the Regional Stress Field on Volcano-Tectonic Orientations",slug:"oki-dozen-dike-swarm-effect-of-the-regional-stress-field-on-volcano-tectonic-orientations",totalDownloads:1494,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"This article presents new field, geochronological, and geochemical data for the Late Miocene Oki-dozen dike swarm (ODS), southwest Japan. This swarm is part of a volcanic suite comprising mafic and silicic dikes, sills, and pyroclastic cones from which we obtained structural measurements at a various genetic orders and scales. The mafic magmas generated three dike swarms with dikes oriented to NW-SE, N-S, and NE-SW. In comparison, the silicic intrusions do not have a preferred orientation but instead appear to radiate from the center of the volcanic suite. Comparison of the maximum thickness of 37 dikes with SiO2 content (wt%) yielded a critical thickness (T\ncr\n) value of T\ncr\n = 0.2 × (SiO2 − 40). These data indicate that the orientations of dikes were controlled by the magnitude of dike tip pressure and magma overpressure, both of which positively correlate with SiO2 concentrations. The silicic units yield estimated pressures (up to 15–60 MPa) that are large enough to have counteracted the regional stress field, whereas the mafic dike swarm only yielded lower pressures. This result suggests that comparative analysis at a range of scales is essential for the accurate determination on the tectonic stress field by igneous rocks.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Daisuke Miura, Kiyoshi Toshida, Ken-ichi Arai, Takeshi Wachi and\nYutaka Wada",authors:[{id:"194873",title:"Dr.",name:"Daisuke",middleName:null,surname:"Miura",slug:"daisuke-miura",fullName:"Daisuke Miura"},{id:"203853",title:"Mr.",name:"Kiyoshi",middleName:null,surname:"Toshida",slug:"kiyoshi-toshida",fullName:"Kiyoshi Toshida"},{id:"203854",title:"Mr.",name:"Ken'Ichi",middleName:null,surname:"Arai",slug:"ken'ichi-arai",fullName:"Ken'Ichi Arai"},{id:"203856",title:"Prof.",name:"Yutaka",middleName:null,surname:"Wada",slug:"yutaka-wada",fullName:"Yutaka Wada"},{id:"204024",title:"Mr.",name:"Takeshi",middleName:null,surname:"Wachi",slug:"takeshi-wachi",fullName:"Takeshi Wachi"}]},{id:"54596",title:"Paleomagnetic Studies on Miocene Sequences of Hokutan and Tottori Groups in Southwest Japan: Implications for Middle Miocene Rotational Movement of Southwest Japan Block Associated with the Japan Sea Opening",slug:"paleomagnetic-studies-on-miocene-sequences-of-hokutan-and-tottori-groups-in-southwest-japan-implicat",totalDownloads:1511,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Miocene sequences composed of volcanic rocks and overlying marine sediments distributing at the Japan Sea side of Southwest Japan have been considered to form related to the rifting and subsequent spreading of the Japan Sea back-arc basin in Miocene time. We performed paleomagnetic investigations on the sequences in the eastern San’in district, the Hokutan and Tottori Groups. Paleomagnetic analyses on samples from 33 sites indicated that characteristic magnetic components from five sites of volcanic rocks in the Hokutan Group and from four sites of marine sediments in the Tottori Group were regarded as primary components. An obtained paleomagnetic direction of the volcanic rocks has an easterly deflected declination (D = 23.9° ± 20.2°), while that of the marine sediments shows no significant deflection in declination (D = 17.8° ± 19.1°). Through the comparison with paleomagnetic data from the Miocene sequences in Southwest Japan, it is suggested that magnetic polarities of the volcanic and sedimentary sequences are assigned to C5Cn and C5Br-C5Bn, respectively, and that the eastern San’in district suffered a clockwise rotation of 24° at around 16 Ma after the early Miocene volcanic activity and before the middle Miocene marine transgression in the whole clockwise rotation process of Southwest Japan related to the Japan Sea opening.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Naoto Ishikawa, Takashi Suzuki and Shiro Ishida",authors:[{id:"194180",title:"Dr.",name:"Naoto",middleName:null,surname:"Ishikawa",slug:"naoto-ishikawa",fullName:"Naoto Ishikawa"},{id:"204504",title:"Dr.",name:"Takashi",middleName:null,surname:"Suzuki",slug:"takashi-suzuki",fullName:"Takashi Suzuki"},{id:"204505",title:"Prof.",name:"Shiro",middleName:null,surname:"Ishida",slug:"shiro-ishida",fullName:"Shiro Ishida"}]},{id:"55296",title:"Alteration Reaction and Mass Transfer via Fluids with Progress of Fracturing along the Median Tectonic Line, Mie Prefecture, Southwest Japan",slug:"alteration-reaction-and-mass-transfer-via-fluids-with-progress-of-fracturing-along-the-median-tecton",totalDownloads:1203,totalCrossrefCites:1,totalDimensionsCites:8,abstract:"We have analyzed mass transfer in the cataclasite samples collected from the Median Tectonic Line, southwest Japan, in which the degree of fracturing is well correlated with the bulk rock chemical compositions determined by the X-ray fluorescence (XRF) analysis. The results of “isocon” analysis indicate not only a large volume increase up to 110% but also the two-stage mass transfer during cataclasis. At the first stage from the very weakly to weakly fractured rocks, the weight percents of SiO2, Na2O, and K2O increase, while those of TiO2, FeO, MnO, MgO, and CaO decrease. At the second stage from the weakly to moderately and strongly fractured rocks, the trend of mass transfer is reversed. The principal component analysis reveals that the variation of chemical compositions in the cataclasite samples can be mostly interpreted by the mass transfer via fluids and by the difference in chemical composition in the protolith rocks to lesser degree. Finally, the changes in the modal composition of minerals with increasing cataclasis analyzed by the X-ray diffraction (XRD) with the aid of “RockJock” software clearly elucidate that the mass transfer of chemical elements was caused by dissolution and precipitation of minerals via fluids in the cataclasite samples.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yumi Kaneko, Toru Takeshita, Yuto Watanabe, Norio Shigematsu\nand Ko‐Ichiro Fujimoto",authors:[{id:"194157",title:"M.Sc.",name:"Yumi",middleName:null,surname:"Kaneko",slug:"yumi-kaneko",fullName:"Yumi Kaneko"},{id:"204607",title:"Prof.",name:"Toru",middleName:null,surname:"Takeshita",slug:"toru-takeshita",fullName:"Toru Takeshita"},{id:"204608",title:"MSc.",name:"Yuto",middleName:null,surname:"Watanabe",slug:"yuto-watanabe",fullName:"Yuto Watanabe"},{id:"204609",title:"Dr.",name:"Norio",middleName:null,surname:"Shigematsu",slug:"norio-shigematsu",fullName:"Norio Shigematsu"},{id:"204610",title:"Dr.",name:"Ko-Ichiro",middleName:null,surname:"Fujimoto",slug:"ko-ichiro-fujimoto",fullName:"Ko-Ichiro Fujimoto"}]},{id:"54454",title:"Structural Features Along the Median Tectonic Line in Southwest Japan: An Example of Multiphase Deformation on an Arc‐Bisecting Fault",slug:"structural-features-along-the-median-tectonic-line-in-southwest-japan-an-example-of-multiphase-defor",totalDownloads:1266,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"A geological survey for the Late Cretaceous Izumi Group distributed on the Median Tectonic Line (MTL) active fault system in the central part of southwestern Japan has revealed varied deformation styles. Among the confined deformation zones found in the western and central parts of the study area, some are located far from the active trace of the MTL (Negoro Fault), at distances of up to 300–350 m. Such kink zones may have been generated during a contraction phase of the MTL from the end of the Pliocene to the early Pleistocene. We identified clear active foldings in a narrow zone sandwiched between a north dextral and a south reverse active fault. Western and eastern upheavals of the crustal sliver show ridge and domal active morphologies, respectively. Structural analysis was extended to the north of the MTL, where the Izumi Group has suffered multiphase deformation since the Cretaceous. The phase stripping method was introduced to extract the neotectonic trend, which successfully delineated complicated deformation zones related to the morphological divergence of the MTL active fault system.",book:{id:"5615",slug:"evolutionary-models-of-convergent-margins-origin-of-their-diversity",title:"Evolutionary Models of Convergent Margins",fullTitle:"Evolutionary Models of Convergent Margins - Origin of Their Diversity"},signatures:"Yasuto Itoh and Tomotaka Iwata",authors:[{id:"46893",title:"Dr.",name:"Yasuto",middleName:null,surname:"Itoh",slug:"yasuto-itoh",fullName:"Yasuto Itoh"},{id:"203882",title:"Prof.",name:"Tomotaka",middleName:null,surname:"Iwata",slug:"tomotaka-iwata",fullName:"Tomotaka Iwata"}]}],onlineFirstChaptersFilter:{topicId:"657",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:288,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). 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Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:43,paginationItems:[{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",doi:"10.5772/intechopen.105052",signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81723",title:"Peroxisomal Modulation as Therapeutic Alternative for Tackling Multiple Cancers",doi:"10.5772/intechopen.104873",signatures:"Shazia Usmani, Shadma Wahab, Abdul Hafeez, Shabana Khatoon and Syed Misbahul Hasan",slug:"peroxisomal-modulation-as-therapeutic-alternative-for-tackling-multiple-cancers",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81638",title:"Aging and Neuropsychiatric Disease: A General Overview of Prevalence and Trends",doi:"10.5772/intechopen.103102",signatures:"Jelena Milić",slug:"aging-and-neuropsychiatric-disease-a-general-overview-of-prevalence-and-trends",totalDownloads:14,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81566",title:"New and Emerging Technologies for Integrative Ambulatory Autonomic Assessment and Intervention as a Catalyst in the Synergy of Remote Geocoded Biosensing, Algorithmic Networked Cloud Computing, Deep Learning, and Regenerative/Biomic Medicine: Further Real",doi:"10.5772/intechopen.104092",signatures:"Robert L. 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Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",institutionURL:null,country:{name:"Hungary"}}}]},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",slug:"antioxidants",publishedDate:"November 6th 2019",editedByType:"Edited by",bookSignature:"Emad Shalaby",hash:"76361b4061e830906267933c1c670027",volumeInSeries:5,fullTitle:"Antioxidants",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby",profilePictureURL:"https://mts.intechopen.com/storage/users/63600/images/system/63600.png",biography:"Dr. Emad Shalaby is a professor of biochemistry on the Biochemistry Department Faculty of Agriculture, Cairo University. He\nreceived a short-term scholarship to carry out his post-doctoral\nstudies abroad, from Japan International Cooperation Agency\n(JICA), in coordination with the Egyptian government. Dr.\nShalaby speaks fluent English and his native Arabic. He has 77\ninternationally published research papers, has attended 15 international conferences, and has contributed to 18 international books and chapters.\nDr. Shalaby works as a reviewer on over one hundred international journals and is\non the editorial board of more than twenty-five international journals. He is a member of seven international specialized scientific societies, besides his local one, and\nhe has won seven prizes.",institutionString:"Cairo University",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}]}]},openForSubmissionBooks:{},onlineFirstChapters:{},subseriesFiltersForOFChapters:[],publishedBooks:{},subseriesFiltersForPublishedBooks:[],publicationYearFilters:[],authors:{paginationCount:617,paginationItems:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNVJQA4/Profile_Picture_2022-03-07T13:23:04.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. degree from Integral University. Currently, he’s working as an Assistant Professor of Pharmaceutics in the Faculty of Pharmacy, Integral University. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than 32 original articles published in reputed journals, 3 edited books, 5 book chapters, and a number of scientific articles published in ‘Ingredients South Asia Magazine’ and ‘QualPharma Magazine’. He is a member of the American Association for Cancer Research, International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs that aim to provide practical solutions to current healthcare problems.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}},{id:"226275",title:"Ph.D.",name:"Metin",middleName:null,surname:"Budak",slug:"metin-budak",fullName:"Metin Budak",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226275/images/system/226275.jfif",biography:"Metin Budak, MSc, PhD is an Assistant Professor at Trakya University, Faculty of Medicine. He has been Head of the Molecular Research Lab at Prof. Mirko Tos Ear and Hearing Research Center since 2018. His specializations are biophysics, epigenetics, genetics, and methylation mechanisms. He has published around 25 peer-reviewed papers, 2 book chapters, and 28 abstracts. He is a member of the Clinical Research Ethics Committee and Quantification and Consideration Committee of Medicine Faculty. His research area is the role of methylation during gene transcription, chromatin packages DNA within the cell and DNA repair, replication, recombination, and gene transcription. His research focuses on how the cell overcomes chromatin structure and methylation to allow access to the underlying DNA and enable normal cellular function.",institutionString:"Trakya University",institution:{name:"Trakya University",country:{name:"Turkey"}}},{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",biography:"Anca Pantea Stoian is a specialist in diabetes, nutrition, and metabolic diseases as well as health food hygiene. She also has competency in general ultrasonography.\n\nShe is an associate professor in the Diabetes, Nutrition and Metabolic Diseases Department, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania. She has been chief of the Hygiene Department, Faculty of Dentistry, at the same university since 2019. Her interests include micro and macrovascular complications in diabetes and new therapies. Her research activities focus on nutritional intervention in chronic pathology, as well as cardio-renal-metabolic risk assessment, and diabetes in cancer. She is currently engaged in developing new therapies and technological tools for screening, prevention, and patient education in diabetes. \n\nShe is a member of the European Association for the Study of Diabetes, Cardiometabolic Academy, CEDA, Romanian Society of Diabetes, Nutrition and Metabolic Diseases, Romanian Diabetes Federation, and Association for Renal Metabolic and Nutrition studies. She has authored or co-authored 160 papers in national and international peer-reviewed journals.",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",country:{name:"Romania"}}},{id:"279792",title:"Dr.",name:"João",middleName:null,surname:"Cotas",slug:"joao-cotas",fullName:"João Cotas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279792/images/system/279792.jpg",biography:"Graduate and master in Biology from the University of Coimbra.\n\nI am a research fellow at the Macroalgae Laboratory Unit, in the MARE-UC – Marine and Environmental Sciences Centre of the University of Coimbra. My principal function is the collection, extraction and purification of macroalgae compounds, chemical and bioactive characterization of the compounds and algae extracts and development of new methodologies in marine biotechnology area. \nI am associated in two projects: one consists on discovery of natural compounds for oncobiology. The other project is the about the natural compounds/products for agricultural area.\n\nPublications:\nCotas, J.; Figueirinha, A.; Pereira, L.; Batista, T. 2018. An analysis of the effects of salinity on Fucus ceranoides (Ochrophyta, Phaeophyceae), in the Mondego River (Portugal). Journal of Oceanology and Limnology. in press. DOI: 10.1007/s00343-019-8111-3",institutionString:"Faculty of Sciences and Technology of University of Coimbra",institution:null},{id:"279788",title:"Dr.",name:"Leonel",middleName:null,surname:"Pereira",slug:"leonel-pereira",fullName:"Leonel Pereira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/279788/images/system/279788.jpg",biography:"Leonel Pereira has an undergraduate degree in Biology, a Ph.D. in Biology (specialty in Cell Biology), and a Habilitation degree in Biosciences (specialization in Biotechnology) from the Faculty of Science and Technology, University of Coimbra, Portugal, where he is currently a professor. In addition to teaching at this university, he is an integrated researcher at the Marine and Environmental Sciences Center (MARE), Portugal. His interests include marine biodiversity (algae), marine biotechnology (algae bioactive compounds), and marine ecology (environmental assessment). Since 2008, he has been the author and editor of the electronic publication MACOI – Portuguese Seaweeds Website (www.seaweeds.uc.pt). He is also a member of the editorial boards of several scientific journals. Dr. Pereira has edited or authored more than 20 books, 100 journal articles, and 45 book chapters. He has given more than 100 lectures and oral communications at various national and international scientific events. He is the coordinator of several national and international research projects. In 1998, he received the Francisco de Holanda Award (Honorable Mention) and, more recently, the Mar Rei D. Carlos award (18th edition). He is also a winner of the 2016 CHOICE Award for an outstanding academic title for his book Edible Seaweeds of the World. In 2020, Dr. Pereira received an Honorable Mention for the Impact of International Publications from the Web of Science",institutionString:"University of Coimbra",institution:{name:"University of Coimbra",country:{name:"Portugal"}}},{id:"61946",title:"Dr.",name:"Carol",middleName:null,surname:"Bernstein",slug:"carol-bernstein",fullName:"Carol Bernstein",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61946/images/system/61946.jpg",biography:"Carol Bernstein received her PhD in Genetics from the University of California (Davis). She was a faculty member at the University of Arizona College of Medicine for 43 years, retiring in 2011. Her research interests focus on DNA damage and its underlying role in sex, aging and in the early steps of initiation and progression to cancer. In her research, she had used organisms including bacteriophage T4, Neurospora crassa, Schizosaccharomyces pombe and mice, as well as human cells and tissues. She authored or co-authored more than 140 scientific publications, including articles in major peer reviewed journals, book chapters, invited reviews and one book.",institutionString:"University of Arizona",institution:{name:"University of Arizona",country:{name:"United States of America"}}},{id:"182258",title:"Dr.",name:"Ademar",middleName:"Pereira",surname:"Serra",slug:"ademar-serra",fullName:"Ademar Serra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/182258/images/system/182258.jpeg",biography:"Dr. Serra studied Agronomy on Universidade Federal de Mato Grosso do Sul (UFMS) (2005). He received master degree in Agronomy, Crop Science (Soil fertility and plant nutrition) (2007) by Universidade Federal da Grande Dourados (UFGD), and PhD in agronomy (Soil fertility and plant nutrition) (2011) from Universidade Federal da Grande Dourados / Escola Superior de Agricultura Luiz de Queiroz (UFGD/ESALQ-USP). Dr. Serra is currently working at Brazilian Agricultural Research Corporation (EMBRAPA). His research focus is on mineral nutrition of plants, crop science and soil science. 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