Open Access is an initiative that aims to make scientific research freely available to all. To date our community has made over 100 million downloads. It’s based on principles of collaboration, unobstructed discovery, and, most importantly, scientific progression. As PhD students, we found it difficult to access the research we needed, so we decided to create a new Open Access publisher that levels the playing field for scientists across the world. How? By making research easy to access, and puts the academic needs of the researchers before the business interests of publishers.
We are a community of more than 103,000 authors and editors from 3,291 institutions spanning 160 countries, including Nobel Prize winners and some of the world’s most-cited researchers. Publishing on IntechOpen allows authors to earn citations and find new collaborators, meaning more people see your work not only from your own field of study, but from other related fields too.
Cancer is undeniably a scary disease that leads to morbidity and mortality. With the state-of-the-art advances, chemotherapy has made incredible strides, but the efficiency is still questionable. Diagnosing and treating cancer are necessary to effectively approach the disease. Theranostics is a hybrid technique that combines therapeutics and diagnostics. The key to cancer therapy is targeted drug delivery, which specifically kills cancer cells without harming healthy cells. The idea of targeted therapy is merely a theoretical expectation that the drug will reach the target site. As seeing is believing, theranostics helps visualize the drug delivery with the combination of diagnostic agents. Clinical settings have extensively examined the field of theranostics. This chapter goes into great length about the potential targets and radioisotopes in theranostics.
Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India
Alagumurugan Alagaraswamy
Research & Development, Maiva Pharma Private Limited, Hosur, Tamil Nadu, India
Muthukumar Subramanian
Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India
Vinesha Ravi
Department of Pharmaceutics, KMCH College of Pharmacy, Coimbatore, Tamil Nadu, India
*Address all correspondence to: gayathrigogul@gmail.com
1. Introduction
Cancer is an intractable condition that has remaining a challenge for patients and physicians for several decades. Cancer is a complex disease that is one of the leading causes of morbidity and mortality worldwide. It is caused due to abnormal behavior of the cells that divide in an unusual manner [1]. According to the World Health Organization, alcohol consumption, tobacco use, diet, chemical exposure, and pollution are the major risk factors for cancer [2]. For the year 2023, the American Cancer Society has anticipated 1,958,310 new cancer cases with a shocking 609,820 deaths associated with cancer [3]. Cancer is conventionally treated by surgery, radiation therapy, chemotherapy, hormonal therapy, and immunotherapy [4, 5]. Despite of the modern advancements, cancer is still a nightmare. Targeting a cancer cell with high specificity is required as the cancer stem cells are responsible for tumor propagation [6]. The resistance developed by the body against the anticancer agents is also considered. Conventional chemotherapeutic agents are generally toxic and less specific in nature. One major noticeable cause is the delay and difficulties in cancer diagnostics. Cancers of the esophagus and pancreas are silent killers as they do not show any early signs for detection [7]. Some recent advances in cancer diagnosis are listed in Table 1.
Theranostics is a combinatory term that combines therapeutics and diagnostics. Theranostic approach enables targeted, quick, and effective treatment, minimizing multi-step procedures in diagnosis and treatment. It is an easier system that allows the switch from diagnostic to therapeutic agent. It is a personalized drug delivery system that can be modified based on the requirements of the patients [8]. For this purpose, radioactive agents and radiotherapeutic approach are used [9].
In order to serve as both diagnostic and therapeutic approaches, theranostic agent is made up of biomarkers with radioactive material. The radioactive nature of the system enables visualization through molecular imaging techniques like Positron Emission tomography (PET), Computerized tomography (CT), and single-photon emission computed tomography (SPECT) [10]. The theranostic targets of common cancers are summarized in Table 2.
Theranostics hold enormous potential in the treatment of cancer. Thyroid cancer is an endocrine malignancy observed among 1% of new cases each year [25]. Radioiodine therapy is a well-established technique used for treating thyroid cancer in post-surgical cases [26]. Radioactive Iodine 131[131I] is the oldest theranostic agent, still being widely used. Uptake of radioactive iodine is promoted by high levels of Thyroid Stimulating Hormone (TSH) [11]. Apart from radioactive iodine [18F] fluoro-D-glucose ([18F] FDG) is another widely used theranostic marker. The theranostic agents target cellular transporters like sodium iodine symporter (NIS), glucose transporter (GT), amino acid transporter (AAT), and nucleoside transporter (NT). NIS facilitates the movement of sodium and iodide ions in and out through the cell membrane. Agents like [131I] and [18F] tetrafluoroborate ([18F] TFB) have a high affinity towards NIS and get transported into the thyroid cancer cells where overexpression can be noticed [12]. Figure 1 shows the comparative visualization of 131Iodine and [18F] Tetrafluoroborate tracers. [18F] fluoro-D-glucose [18F] FDG, being a glucose analog, is transported through GT and visualized by PET scan [13]. In some cases, [18F] FDG yields false positive results, to address that alternate AAT targeting agents like L-[methyl-11C]-methionine ([11C] MET), and [18F] fluor glutamine ([18F] FL) are gaining attention [14]. It is also noticeable that NT targeting agents are still being studied and remain in the development stage.
Figure 1.
Comparison of 131Iodine and [18F] Tetrafluoroborate tracers [13].
2.2 Neuro-endocrine cancer
Iodine-131-meta-iodobenzylguanidine is a form of radiotherapy that contains meta-iodobenzylguanidine (MIBG) with trace amounts of radioactive iodine. MIBG is a guanidine derivative used for imaging and therapy of neuroendocrine tumors and neuroblastoma [15, 27]. Neuroblastoma is pictured by extracranial tumors. MIBG is the preferred diagnostic agent as it exhibits high specificity and selectivity [28]. 123I-MIBG and 131I-MIBG are used in clinical imaging studies, more effective in stage IV neuroblastoma as they offer better visibility [29]. As the I-MIBG structurally resembles norepinephrine, it is easily taken up by the neuroendocrine cells [16, 17]. However, it must be brought to attention that acute thyroid blockade is necessary before I-MIBG use, as the iodine complex is most likely absorbed by the thyroid glands [30]. 18F-fluorodeoxyglucose-based PET/CT scans are employed in the case of early-stage neuroblastoma [31].
2.3 Pancreatic cancer
Pancreatic cancer is the deadliest form of cancer. Pancreatic cancer is usually asymptomatic or exhibits minimal symptoms, making it difficult to diagnose in its initial stages. Theranostics is a sensible approach for efficient diagnosis and treatment of cancer that has a very low survival rate [32]. CA19.9 (cancer antigen 19.9), MUC1 (glycoprotein mucin 1), and TAG72 (tumor-associated glycoprotein 72) have been the major targets for pancreatic cancer theranostics [18, 23].
2.4 Prostate cancer
Cancer of the prostate is the second most common type of cancer occurring in men. The etiology of prostate cancer is less known compared to other types of cancers. The risk factors include age, lifestyle, diet, chemical exposure, obesity, infection, and more [33, 34]. The first line treatment of prostate cancer is targeting the 5-α reductase enzyme. The 5-α reductase is responsible for conversion of testosterone to dihydrotestosterone, which promotes prostate cancer. 5-α reductase inhibitors like finasteride are effective chemo-preventive agents [35, 36]. Along with this, androgen-depriving agents and chemotherapy can be employed. In recent years, hormonal agents, namely abiraterone and enzalutamide, depicted better results [37].
Prostate-specific membrane antigen (PSMA), also known as glutamate carboxypeptidase II, is a membrane-bound glycoprotein that is normally found in healthy prostate cells but is present in abnormally high concentrations in prostate cancer [38]. PSMA imaging acts as a vital diagnostic tool in prostate cancer. PSMA radioligand therapy (PRLT) is a technique where ligands associated with PSMA are combined with a radioactive isotope to serve as a theranostic agent [39]. In recent years, PSMA has been visualized using radioactive nuclei like 68Ga, 99mTc, and 123/124/131-I. 68Ga radiopharmaceutical is the first FDA-approved gallium system for PET imaging prostate cancer in 2020. PSMA 11 is of major focus in prostate cancer.
[68Ga]Ga-PSMA-11 is widely used for initial diagnosis, prostate cancer staging, and metastases. It is formed by complexation of Ga with hexadentate chelator with octahedral geometry. It has relatively short half-life of about 67.6 minutes. Now [68Ga] Ga-PSMA-11 is available as ready-to-use injectable solution [19].
Hofman et al., studied and reported that the [68Ga] Ga-PSMA-11 has excellent specificity and selectivity compared to conventional imaging techniques [40]. Bombesin is a prostate cancer growth factor, overexpressed in malignancy. Bombesin is coupled with technetium-99 m which serves as a theranostic agent to detect and stage prostate cancer. Scopinaro et al., mentioned that the use of 99mTC-Bombesin is sufficiently high for diagnosing prostate cancer [41]. Morris et al., combined anticancer agent docetaxel with radium-223 which was well tolerated and might have efficacy compared to docetaxel alone [42, 43].
2.5 Breast cancer
Breast cancer is a deadly form of cancer that concerns the women population. The happy relief is that about 80% of the breast cancer is curable [44]. Breast biopsy is the ultimate method of diagnosing breast cancer, however, imaging studies such as mammography and MRI are prominent tools [45].
The oncogene of breast cancer, HER2 (human epidermal growth factor receptor 2) can be targeted through trastuzumab radiolabeled with Indium-111, Cu-trastuzumab, and [89Zr] Zr-trastuzumab. Coupling monoclonal antibodies such as trastuzumab with 177Lu and bifunctional chelating agents enables HER2 targeting. Lu is a gamma emitter which comes with minimal toxicity [20, 21]. 177Lutetium- [DOTA°, Tyr3] octreotate (177Lu-DOTATATE) is an FDA-approved radionucleotide therapy, recommended for gastropancreatic neuroendocrine tumors [22]. Fibroblast activation protein (FAP) is expressed in cancer-associated fibroblasts. FAP inhibitors are preferred for their diagnostic and therapeutic value [46]. Jokar et al., reported that five patients who demonstrated relapse under conventional therapy responded well with 177Lu-trastuzumab (Herceptin), 177Lu-DOTATATE, and 177Lu-FAPI-46 [47].
To develop a robust diagnostic tool, theranostics revolves around specific targets. One of the recent advancements is using radioactive ligands to target human epidermal growth factor receptor 2 (HER-2) in breast cancer [48]. Anti-HER2 therapy is widely used in the treatment of breast cancer [49]. Trastuzumab is an anti-HER2 monoclonal antibody. Trastuzumab is coupled with radioactive isotope to promote a highly specific diagnostic aid [50]. Indium-111 with trastuzumab is used in SPECT with remarkable results [51].
Copper-64 is another positron-emitting radionuclide that has a preferable half-life, making it a vital diagnostic agent, compared to other radioactive isotopes [52]. Carrasquillo et al., studied the use of [64Cu] Cu-trastuzumab in detecting breast cancer and its brain metastasis and concluded that it is safe, practical, and effective [52]. Zirconium is a radioactive metal with the longest half-life [52]. Dijkers et al., brought to interesting notice that [89Zr] Zr-trastuzumab was sufficient to assess the tumors even after 4–5 days post single-dose injection. However, it is dose dependent and accumulation was observed to increase with time [53].
Beylergil et al., used F(ab′), a fragment of immunoglobulin G, with 1,4,7,10-tetraazacyclododecane-N, N′, N′′, N′′′-tetra acetic acid (DOTA) and trastuzumab and synthesized DOTA-F(ab′)2-trastuzumab. It is further radiolabelled with 68Ga. 68Ga DOTA-F(ab′)2-trastuzumab and reported that the reagent was safe with favorable pharmacokinetics [54].
Guo et al., developed an Iodine-124 coupled trastuzumab for noninvasive PET imaging. It is evident that 124I-Trastuzumab had high tumor uptake and can be used in diagnosis of HER2-positive cancer [55]. Bhusari et al., used 177Lu-trastuzumab to target HER-2 and described its active intake in HER-2 positive breast cancer [56].
2.6 Ovarian cancer
Cancer of the ovaries is one of the lethal forms of cancer. Despite its invasiveness, due to a lack of suitable biomarkers, it goes undiagnosed in early stages. Delayed diagnosis leads to impaired treatment. Near-infrared photoimmunotherapy is a theranostic approach in which a conjugate of antibody and photo absorber. This targets the cancer cells and enables visualization with the support of infrared light [57]. Recurrent ovarian cancer is resistant to traditional therapy. 89Zr-DFO-mAb-B43.13, 89Zr-trastuzumab, and PLGA-RbCur-gadolinium complex are some examples of theranostic agents used to target, folate receptors, CA125, and HER2 involved in ovarian cancers [58].
CA125 is a cancer antigen over-expressed in ovarian cancer. It acts as a remarkable target cell in cancer theranostics. Antibodies specific to CA125 are used in PET imaging [23]. Zirconium is coupled with an anti-CA125 antibody and evaluated in animal models by Sharma et al. [59] 99mTc is also widely explored in ovarian cancer theranostics.
Zeevaart et al., produced 195Pt-Cisplatinum as a part of phase 0 clinical trial. They emphasized that 195Pt-Cisplatinum could serve as a highly specific diagnostic tool with good specificity [24]. Astatine is an alpha emitter used in diagnostics. Hallqvist et al., formed 211At-monoclonal murine antibody complex to target and treat small tumors. The agent was administered as an intraperitoneal injection to patients who exhibited only low-grade toxicity [60].
Radionuclides are the heart of theranostics. To enable visualization, radioisotopes are necessary. Radionuclides can be identified as alpha, beta, or gamma emitters. Alpha emitters usually transfer high energy to the target tumor with a short range of 50–100 μm, so that it does not affect the surrounding cells [61]. Radium-223 (223Ra) decay and thorium-227 (227Th) are the commonly used alpha emitters [62].
Beta emitters are found to have high energy that ends up damaging the DNA and causing cell death [63]. The most commonly used radionuclides are gamma emitters. Gamma emitters produce good-quality imaging via planar imaging or SPECT [60]. The most seen radioisotopes are 123,124I/131I, 99mTc, 43,44Sc/46,47Sc,60,61,64Cu, 68Ga, 177Lu, and 197Au/198Au in some cases [64].
Copper is available in four isotopic forms 67Cu, 64Cu, 61Cu, and 60Cu. Copper is a metal present in micro quantity in human body. It is learned that accumulation of copper is more common in malignant tissues than in normal tissues. This favors the tumor-targeted approach [65, 66]. Copper-based theranostic agents are more specific, pure, and easy to produce.
Gallium, mainly 68Ga, has a long-standing history in theranostics. It is a beta emitter more frequently used in cancer theranostics, involving various organs. 68Ga has half-life of 68.1 minutes. Gallium is also used in combination with chelating agents. 68Ga-DOTATATE injection NETSPOT was approved by USFDA in 2016 for imaging neuroendocrine tumors [67, 68].
Radioactive iodine is ideally one of the first radionuclides used in theranostics. 131I is used in diagnosing thyroid diseases. 124I is prominently employed in detecting thyroid cancer. Therapeutically 131I is also used in tumor hypoxia [69].
Lutetium-177 is a gamma emitter that is desirable in cancer theranostics. It can emit both particulate and electromagnetic radiation, which enables spontaneous imaging and treatment [70].
All the theranostic agents require a visualizing aid to the provide diagnosis. The success of every theranostic agent lies in the apt diagnostic aid. PET is one such technique that is enormously used in cancer diagnosis. Since the ninteenth century, several hybrid visualization techniques such as SPECT-PET have been extensively used [71]. The tracers are exclusively tailor-made to suit the PET imaging. The agents have to facilitate imaging and have suitable pharmacokinetic properties [72]. A thorough in vivo validation has to be performed for theranostic PET agents.
Currently, there are multiple theranostic agents being studied at pre-clinical and clinical levels. Focusing on the recent preclinical development in cancer theranostics, HER3 overexpression can result in resistance against cancer therapy. Andersson et al., developed a radiolabeled anti-HER3 affibody 111In-HEHEHE-Z08698-NOTA which exhibited impressive affinity towards HER3 receptor [73]. Cobalamin is another interesting agent currently in preclinical research. Kuda-Wedagedara et al. used 89Zr to radiolabel cobalamin and used it in PET imaging [74]. Nanotechnology is a well-established drug delivery approach. Despite the advancements, it is surprising that no nano-theranostic agent has been approved by USFDA to date. This is explained through translation difficulties existing in preclinical to clinical conversion of nano-theranostics [75].
The success of any therapeutic, diagnostic, or theranostic agent lies in its safety and efficacy. Despite its attractions, theranostics come with safety concerns due to the use of radioactive agents. Potential toxicity, incompatibilities, and interactions are to be established. Nuclear medicines are complex in terms of production, handling, and administration. Speaking in terms of cost, theranostic agents require special production facilities for handling radioactive, sophisticated instruments, skilled personnel, and critical training [76]. Launching a new drug into the market is an expensive licensing process. When it comes to the theranostic agent, the marginal cost multiplies. Quality and reproducibility must be compliant for each batch. Commercialization also adds to the cost.
Translating a theranostic agent to clinical use is quite a hurdle. The concept of one dose is not applicable in theranostics. The patient-dependent tailoring may rise as a challenge during clinical and regulatory approvals [77].
Theranostics is a fancy term with enormous potential to serve as a novel approach to deadly diseases like cancer. It aids in early diagnosis and treatment of silent cancers, as time is the ultimate. Combining a diagnostic and therapeutic agent minimizes the cost, duration, and labor in individual therapy. Falling under personalized medicine, theranostics provide patient-tailored drug delivery with specific dosimetry. Radionuclides provide visibility and promote easy diagnosis of complex tumors. Speaking beyond the advantages, theranostics is still a questionable approach based on its safety and efficacy. It is challenging both in terms of production and clinical setting. We draw a firm conclusion that theranostics is a potential tool in cancer detection and treatment and it should come with uncompromised safety.
1.Wu S, Zhu W, Thompson P, Hannun YA. Evaluating intrinsic and non-intrinsic cancer risk factors. Nature Communications. 2018;9(1):3490
2.Internet Source – Cancer, WHO Factsheets. Available from: https://www.who.int/news-room/factsheets/detail/cancer#:~:text=Tobacco%20use%2C%20alcohol%20consumption%2C%20unhealthy,%2D%20and%20middle%2Dincome%20countries [Accessed: April 16, 2023]
3.Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA: A Cancer Journal for Clinicians. 2023;73(1):17-48
4.Park W, Heo YJ, Han DK. New opportunities for nanoparticles in cancer immunotherapy. Biomaterial Research. 2018;22:24
5.Gavas S, Quazi S, Karpiński TM. Nanoparticles for cancer therapy: Current progress and challenges. Nanoscale Research Letters. 2021;16:173
6.Copland M, Jorgensen HG, Holyoake TL. Evolving molecular therapy for chronic myeloid leukemia-are we on target? Hematology. 2005;10:349-359
7.Chakraborty S, Rahman T. The difficulties in cancer treatment. E Cancer Medical Science. 2012;6:ed16
8.Jeelani S, Reddy RC, Maheswaran T, Asokan GS, Dany A, Anand B. Theranostics: A treasured tailor for tomorrow. Journal of Pharmacy & Bioallied Sciences. 2014;6(Suppl. 1):S6-S8
9.Okamoto S, Shiga T, Tamaki N. Clinical perspectives of theranostics. Molecules. 2021;26(8):2232
10.Pinto JT, Suffoletto BP, Berzin TM, Qiao CH, Lin S, Tong WP, et al. Prostate-specific membrane antigen: A novel folate hydrolase in human prostatic carcinoma cells. Clinical Cancer Research. 1996;2:1445-1451
11.Choudhury PS, Gupta M. Differentiated thyroid cancer theranostics: Radioiodine and beyond. The British Journal of Radiology. 2018;91(1091):20180136
12.Concilio SC, Zhekova HR, Noskov SY, Russell SJ. Inter-species variation in monovalent anion substrate selectivity and inhibitor sensitivity in the sodium iodide symporter (NIS). PLoS One. 2020;15:e0229085
13.Samnick S, Al-Momani E, Schmid J-S, Mottok A, Buck AK, Lapa C. Initial clinical investigation of [18F]Tetrafluoroborate PET/CT in comparison to [124I]iodine PET/CT for imaging thyroid cancer. Clinical Nuclear Medicine. 2018;43:162-167
14.Jochumsen MR, Iversen P, Arveschoug AK. Follicular thyroid cancer avid on C-11 methionine PET/CT. Endocrinology Diabetes Metabolism Case Report. 2018:17-0151
15.Agrawal A, Rangarajan V, Shah S, Puranik A, Purandare N. MIBG (metaiodobenzylguanidine) theranostics in pediatric and adult malignancies. The British Journal of Radiology. 2018;91(1091):20180103
16.Dhull VS, Sharma P, Patel C, Kundu P, Agarwala S, Bakhshi S, et al. Diagnostic value of 18F-FDG PET/CT in paediatric neuroblastoma: Comparison with 131I-MIBG scintigraphy. Nuclear Medicine Communication. 2015;36:1007-1013
17.Filippi L, Frantellizzi V, Sidrak MMA, Gorica J, Scippa S, Chiaravalloti A, et al. Radiotheranostic agents targeting neuroblastoma: State-of-the-art and emerging perspectives. Oncology. 2021;1(2):123-139
18.Jaidev LR, Chede LS, Kandikattu HK. Theranostic nanoparticles for pancreatic cancer treatment. Endocrine, Metabolic & Immune Disorders Drug Targets. 2021;21(2):203-214
19.Eder M, Neels O, Müller M, Bauder-Wüst U, Remde Y, Schäfer M, et al. Novel preclinical and radiopharmaceutical aspects of [68Ga]Ga-PSMA-HBED-CC: A new PET tracer for imaging of prostate cancer. Pharmaceuticals. 2014;7:779-796
20.Jadvar H, Chen X, Cai W, Mahmood U. Radiotheranostics in cancer diagnosis and management. Radiology. 2018;286:388-400
21.Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, et al. Breast cancer (primer). Nature Reviews: Disease Primers. 2019;5:66
22.Signore A, Lauri C, Auletta S, Varani M, Onofrio L, Glaudemans AW, et al. Radiopharmaceuticals for breast cancer and neuroendocrine tumors: Two examples of how tissue characterization may influence the choice of therapy. Cancers. 2020;12:781
23.Nimmagadda S, Penet MF. Ovarian cancer targeted theranostics. Frontier in Oncology. 2020;9:1537
24.Zeevaart JR, Wagener J, Marjanovic-Painter B, Sathekge M, Soni N, Zinn C, et al. Production of high specific activity 195mPt-cisplatinum at South African Nuclear Energy Corporation for Phase 0 clinical trials in healthy individual subjects. Journal of Labelled Compounds and Radiopharmaceuticals. 2013;56(9-10):495-503
25.Greco A, Miranda C, Borrello MG, Pierotti MA. Thyroid cancer. Cancer Genomics. 2014;5:265-280
26.Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;26:1-133
27.Yoshinaga K, Abe T, Okamoto S, Uchiyama Y, Manabe O, Ito YM, et al. Effects of repeated 131I-meta-iodobenzylguanidine radiotherapy on tumor size and tumor metabolic activities in patients with metasatic neuroendocrine tumors. Journal of Nuclear Medicine. 2020;62(5)685-694
28.Lumbroso J, Guermazi F, Hartmann O, Coornaert S, Rabarison Y, Lemerle J, et al. Sensitivity and specificity of meta-iodobenzylguanidine (mIBG) scintigraphy in the evaluation of neuroblastoma: Analysis of 115 cases. Bulletin du Cancer. 1988;75:97-106
29.Monsieurs M, Brans B, Bacher K, Dierckx R, Thierens H. Patient dosimetry for 131I-MIBG therapy for neuroendocrine tumours based on 123I-MIBG scans. European Journal of Nuclear Medicine and Molecular Imaging. 2002;29:1581-1587
30.Jha P, Frölich AMJ, McCarville B, Navarro OM, Babyn P, Goldsby R, et al. Unusual association of alveolar rhabdomyosarcoma with pancreatic metastasis: Emerging role of PET-CT in tumor staging. Pediatric Radiology. 2010;40:1380-1386
31.Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: A Cancer Journal for Clinicians. 2019;69:7-34
32.King J, Bouvet M, Singh G, Williams J. Improving theranostics in pancreatic cancer. Journal of Surgical Oncology. 2017;116(1):104-113
33.Barca C, Griessinger CM, Faust A, Depke D, Essler M, Windhorst AD, et al. Expanding Theranostic radiopharmaceuticals for tumor diagnosis and therapy. Pharmaceuticals (Basel). 2021;15(1):13
34.Pienta KJ, Esper PS. Risk factors for prostate cancer. Annals of Internal Medicine. 1993;118(10):793-803
35.Rawla P. Epidemiology of prostate cancer. World Journal of Oncology. 2019;10(2):63-89
36.Walsh PC, Madden JD, Harrod MJ, Goldstein JL, MacDonald PC, Wilson JD. Familial incomplete male pseudohermaphroditism, type 2. Decreased dihydrotestosterone formation in pseudovaginal perineoscrotal hypospadias. The New England Journal of Medicine. 1974;291(18):944-949
37.Attard G, Belldegrun AS, De Bono JS. Selective blockade of androgenic steroid synthesis by novel lyase inhibitors as a therapeutic strategy for treating metastatic prostate cancer. BJU International. 2005;96:1241-1246
38.Jang A, Kendi AT, Sartor O. Status of PSMA-targeted radioligand therapy in prostate cancer: Current data and future trials. Therapeutic Advanced Medical Oncology. 2023;15:17588359231157632
39.Bois F, Noirot C, Dietemann S, Mainta IC, Zilli T, Garibotto V, et al. [68Ga]Ga-PSMA-11 in prostate cancer: A comprehensive review. American Journal of Nuclear Medicine and Molecular Imaging. 2020;10(6):349-374
40.Hofman MS, Lawrentschuk N, Francis RJ, Tang C, Vela I, Thomas P, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): A prospective, randomised, multicentre study. Lancet. 2020;395:1208-1216
41.Scopinaro F, De Vincentis G, Varvarigou AD, et al. 99mTc-bombesin detects prostate cancer and invasion of pelvic lymph nodes. European Journal of Nuclear Medicine and Molecular Imaging. 2003;30:1378-1382
42.Morris MJ, Loriot Y, Sweeney CJ, et al. Radium-223 in combination with docetaxel in patients with castration-resistant prostate cancer and bone metastases: A phase 1 dose escalation/randomised phase 2a trial. European Journal of Cancer. 2019;114:107-116
43.O’Dwyer E, Bodei L, Morris MJ. The role of theranostics in prostate cancer. Seminars in Radiation Oncology. 2021;31(1):71-82
44.Siegel RL, Miller KD, Jemal A. Cancer statistics. CA: A Cancer Journal of Clinicians. 2020;70:7-30
45.Nounou MI, ElAmrawy F, Ahmed N, Abdelraouf K, Goda S, Syed-Sha-Qhattal H. Breast cancer: conventional diagnosis and treatment modalities and recent patents and technologies. Breast Cancer (Auckland). 2015;9(Suppl. 2):17-34
46.Kameswaran M, Pandey U, Gamre N, Sarma HD, Dash A. Preparation of 177Lu-Trastuzumab injection for treatment of breast cancer. Applied Radiation and Isotopes. 2019;148:184-190
47.Jokar N, Velikyan I, Ahma-dzadehfar H, Rekabpour SJ, Jafari E, Ting HH, et al. Theranostic approach in breast cancer: A treasured tailor for future oncology. Clinical Nuclear Medicine. 2021;46(8):e410-e420
48.Gaykema SB, de Jong JR, Perik PJ, Brouwers AH, Schröder CP, Munnink THO, et al. (111) In-trastuzumab scintigraphy in HER2-positive metastatic breast cancer patients remains feasible during trastuzumab treatment. Molecular Imaging. 2014;13:5
49.Anthony LB, Woltering EA, Espenan GD, et al. Indium-111-pentetreotide prolongs survival in gastroenteropancreatic malignancies. Seminars in Nuclear Medicine. 2002;32(2):123-132
50.Das S, Al-Toubah T, El-Haddad G, Strosberg J. 177Lu-DOTATATE for the treatment of gastroenteropancreatic neuroendocrine tumors. Expert Review of Gastroenterology & Hepatology. 2019;13(11):1023-1031
51.Wikberg ML, Edin S, Lundberg IV, et al. High intratumoral expression of fibroblast activation protein (FAP) in colon cancer is associated with poorer patient prognosis. Tumour Biology. 2013;34:1013-1020
52.Carrasquillo JA, Morris PG, Humm JL, Smith-Jones PM, Beylergil V, Akhurst T, et al. Copper-64 trastuzumab PET imaging: A reproducibility study. The Quarterly Journal of Nuclear Medicine and Molecular Imaging. 2019;63(2):191-198
53.Dijkers E, Oude MT, Kosterink J, Brouwers A, Jager P, De Jong J, et al. Biodistribution of 89Zr-trastuzumab and PET imaging of HER2-positive lesions in patients with metastatic breast cancer. Clinical Pharmacology and Therapeutics. 2010;87:586-592
54.Beylergil V, Morris PG, Smith-Jones PM, Modi S, Solit D, Hudis CA, et al. Pilot study of 68Ga-DOTA-F(ab’)2-trastuzumab in patients with breast cancer. Nuclear Medicine Communications. 2013;34(12):1157-1165
55.Guo X, Zhou N, Chen Z, Liu T, Xu X, Lei X, et al. Construction of 124 I-trastuzumab for noninvasive PET imaging of HER2 expression: From patient-derived xenograft models to gastric cancer patients. Gastric Cancer. 2020;23:614-626
56.Bhusari P, Vatsa R, Singh G, Parmar M, Bal A, Dhawan DK, et al. Development of Lu-177-trastuzumab for radioimmunotherapy of HER2 expressing breast cancer and its feasibility assessment in breast cancer patients. International Journal of Cancer. 2017;140(4):938-947
57.Sato K, Hanaoka H, Watanabe R, Nakajima T, Choyke PL, Kobayashi H. Near infrared photoimmunotherapy in the treatment of disseminated peritoneal ovarian cancer. Molecular Cancer Therapeutics. 2015;14:141-150
58.Scholler N, Urban N. CA125 in ovarian cancer. Biomarkers in Medicine. 2007;1:513-523
59.Sharma SK, Sevak KK, Monette S, Carlin SD, Knight JC, Wuest FR, et al. Preclinical 89Zr immuno-PET of high-grade serous ovarian cancer and lymph node metastasis. Journal of Nuclear Medicine. 2016;57:771-776
60.Hallqvist A, Bergmark K, Bäck T, Andersson H, Dahm-Kähler P, Johansson M, et al. Intraperitoneal α-emitting radioimmunotherapy with 211AT in relapsed ovarian cancer: Long-term follow-up with individual absorbed dose estimations. Journal of Nuclear Medicine. 2019;160(8):1073-1079
61.Pandit-Taskar N. Targeted radioimmunotherapy and theranostics with alpha emitters. Journal of Medical Imaging and Radioactive Science. 2019;50(4 Suppl 1):S41-S44
62.Staudacher AH, Bezak E, Borysenko A, Brown MP. Targeted alpha-therapy using 227Th-APOMAB and cross-fire antitumour effects: Preliminary in-vivo evaluation. Nuclear Medicine Communications. 2014;35:1284-1290
63.Drude N, Tienken L, Mottaghy FM. Theranostic and nanotheranostic probes in nuclear medicine. Methods. 2017;130:14-22
64.Yordanova A, Eppard E, Kürpig S, Bundschuh RA, Schönberger S, Gonzalez-Carmona M, et al. Theranostics in nuclear medicine practice. Oncotargets and Therapy. 2017;10:4821-4828
65.Denoyer D, Masaldan S, La Fontaine S, Cater M. Targeting copperin cancer therapy: ‘Copper that Cancer’. Metallomics. 2015;7:1459-1476
66.Shanbhag VC, Gudekar N, Jasmer K, Papageorgiou C, Singh K, Petris MJ. Copper metabolism as a unique vulnerability in cancer. Biochimica Biophysica Acta Molecular Cell Research. 2021;1868:118893
67.Raj N, Reidy-Lagunes D. The role of 68Ga-DOTATATE positron emission tomography/computed tomography in well-differentiated neuroendocrine tumors: A case-based approach illustrates potential benefits and challenges. Pancreas. 2018;47:1-5
68.Choiński J, Łyczko M. Prospects for the production of radioisotopes andradiobioconjugates for theranostics. Bio-Algorithms and Med-Systems. 2021;17(4):241-257
69.Silberstein EB. Radioiodine: The classic theranostic agent. Seminars in Nuclear Medicine. 2012;42(3):164-170
70.Gomes Marin JF, Nunes RF, Coutinho AM, Zaniboni EC, Costa LB, Barbosa FG, et al. Theranostics in nuclear medicine: Emerging and re-emerging integrated imaging and therapies in the era of precision oncology. Radiographics. 2020;40(6):1715-1740
71.Cal-Gonzalez J, Rausch I, Shiyam Sundar LK, Lassen ML, Muzik O, Moser E, et al. Hybrid imaging: Instrumentation and data processing. Frontier in Physics. 2018;6:47
72.Van Dongen GA, Poot AJ, Vugts DJ. PET imaging with radiolabeled antibodies and tyrosine kinase inhibitors: Immuno-PET and TKI-PET. Tumour Biology. 2012;33:607-615
73.Andersson KG, Rosestedt M, Varasteh Z, Malm M, Sandström M, Tolmachev V, et al. Comparative evaluation of 111In-labeled NOTA-conjugated affibody molecules for visualization of HER3 expression in malignant tumors. Oncology Reports. 2015;34(2):1042-1048
74.Kuda-Wedagedara ANW, Workinger JL, Nexo E, Doyle RP, Viola-Villegas N. 89Zr-cobalamin PET tracer: Synthesis, cellular uptake, and use for tumor imaging. ACS Omega. 2017;2(10):6314-6320
75.Johnson KK, Koshy P, Yang J, Sorrell CC. Preclinical cancer theranostics—From nanomaterials to clinic: The missing link. Advanced Functional Materials. 2021;31(43):1-40
76.Nunn AD. The cost of bringing a radiopharmaceutical to the patient’s bedside. Journal of Nuclear Medicine. 2007;48:169
77.Dreifuss T, Betzer O, Shilo M, Popovtzer A, Motiei M, Popovtzer R. A challenge for theranostics: Is the optimal particle for therapy also optimal for diagnostics? Nanoscale. 2015;7(37):15175-15184
Written By
Gayathri Rajaram, Alagumurugan Alagaraswamy, Muthukumar Subramanian and Vinesha Ravi
Submitted: 30 May 2023Reviewed: 08 November 2023Published: 01 March 2024
Open access peer-reviewed chapter - ONLINE FIRST
