3.1.1. Standardization: principle and applications
Quality control for the quantification of radiopharmaceutical activity is critical for accurate dosimetry calculations, from whole body to cell microscopy. Tumor uptake of radiopharmaceutical need to be correlated with tumor response and to be related to the tumor radiation absorbed dose. 
|Isotope||Major decay modes||Method for standardization||Detection efficiency (ε)||Activity accuracy & uncertainty (U)||Ref.|
|-||β, γ, β-γ, EC, EC-γ, α, and mixed decay nuclides||LSC and C/N method||εpure γ: ~100%|
εpure EC: < 75%
|U: 0.2-0.5% (pure β)|
U: 0.2-0.5% (β-γ)
|Co-57||EC decay to Fe-57||4πβ-γ coincidence method||ε: ~75%||U: 2%||50|
4πβ-γ coincidence method
|To ground state: β+ (87.85%), EC (8.92%)|
To 1077 keV: β+ (1.29%), EC (1.93%)
Annihilation radiation: 178.29%
γ-ray to 1077 keV: 3.22%
|1. Ge-68||EC decay to Zn-68|
|2. Ga-68||β+, EC, γ decay to Zn-68|
|Sn-117m- DTPA||Decay to Sn-117||4πβ LS and 4πγ methods||UC: 0.60% (for DTPA by LS)|
UC: 2.43% (for DTPA by NaI(T1))
|Cs-131||EC decay to Xe-131||Coincidence methods: L Auger electrons plus L X-rays and K X-rays||-||U: 1%||53|
|Cs-134||β- and γ decay to Ba-134||LSC||ε: ~95%||3191 ± 8 kBq/g (0.54%)||54|
|4πβ-γ coincidence method||ε: 65-87%||3194 ± 12 kBq/g (0.88%)|
|4πγ method||ε: ~83%||3174 ± 25 kBq/g (2.09%)|
|Tl-201||γ decays to Hg-201||High-pressure IC|
4πγ coincidence method
|γ ray (167.4 keV) probability: 0.1000 ± 0.0006||7.207 ± 0.033 (NIST)|
7.197 ± 0.027 (NPL)
7.116 ± 0.050 (PTB)
|Tl-204||β- decay (97.4%) to Pb-204 and EC decay (2.6%) to Hg-204||Windowless 4π-CsI(Tl) -sandwich spectrometer, LSC, PPC||56|
|4πβ-γ coincidence method and Cs-134 tracer||εβ: 71 - 91%|
εEC (~ εAEs): 50 - 100%
|Pb-210||β decay to Bi-210 (t1/2 5.103 d), Po-210 (t1/2 138.4 d), and α decay to Pb-206||4πβ-γ coincidence method|
Germanium γ spectrometry
Some examples of absolute standardization of radiopharmaceuicals and related radioisotopes [17,50-58]
The theoretical counting efficiency, i.e. counts/disintegration or counts per minute/disintegration per minute (cpm/dpm), for a radionuclide can be used to examine the absolute activity, in disintegration or disintegration per minute (dpm) of the radionuclide. Different efficiency tracing methods has been developed for more than six decade by characterizing the effects of sample volume, medium composition (matrix), pulse discrimination conditions, photomultiplier voltage, amplifier gain, and luminophor concentration on counting efficiency of a radioactive species . The use of 4πβ scintillation counting and 4πβ-γ coincidence counting for the standardization of certain electron capture (EC) nuclides with simple decay schemes is established since 1952  and 1957 .
Some examples of absolute standardization of radiopharmaceuicals and related radioisotopes are shown in Table 2 [17,50-58]. Below, we introduce different tracing methods, including (a) efficiency tracing (and extrapolation) method using a non-H-3 standard solution, (b) CIEMAT-NIST (C/N) efficiency tracing method, (c) non-extrapolation tracer method, (d) coincidence method by a 4πβ-γ system, (e) triple to double coincidence ratio (TDCR) method, and (f) 4πγ counting method.
(a) The efficiency tracing (and extrapolation) method using a non-H-3 standard solution
The efficiency tracer techniques, using Co-60, Cs-134, C-14, Cr-51, Mn-54 or Am-241 standard solution for the standardization of the β-γ nucides were developed. The 4π liquid scintillation (LS) consisted of the extrapolation of the 4π counting rate to the zero discrimination level for the standardization of the Tl-204 (97.6% β emission and 2.4% electron capture) solution was carried out for efficiency tracing using a Co-60 standard solution received in the framework of the 1997 BIPM comparison was carried out by Sahagia et al. . A germanium spectrometer was calibrated for the standardization of Pb-210 using Am-241 as a normalizing agent has been proposed . Instead, Dias et al. chose Cs-134 as an efficiency tracer to standardize Tl-204 as well as a 4πβ-γ coincidence system for the calibration . This method can be also successfully used for the standardization of radionuclides such as Ir-192, Zn-65, Mn-54, with the detection of the β rays, Auger electrons, X rays, in the proportional counter (PC) . Efficiency tracing with C-14 and zero detection threshold techniques with H-3 as tracers was applied for standardization of various β-emitting radionuclides, e.g. C-14, Cl-36, and Tl-204 using LS spectrometer .
Recently, different methodologies were proposed. Koskinas et al. developed a “dual-tracers”, e.g. Cr-51 and Mn-54 procedure followed by the Laboratório de Metrologia Nuclear (LMN) for the standardization of EC nuclide, i.e. Fe-55. The efficiency was obtained by selecting a γ-ray window set at 320 keV (Cr-51) and at 834 keV (Mn-54) . The activity of EC radionuclides is usually determined by 4π (proportional counter, PC)-γ coincidence counting and by an efficiency extrapolation method. However, an alternative method, called “wet extrapolation method”, utilizes an absorption change during the drying of a water droplet added onto the source surface, variation of the PC detection efficiency can be achieved. Slopes of extrapolation curves and resulting activity values obtained are compared for several radionuclides (Mn-54, Ce-139, Y-88, and Co-57) .
(b) The CIEMAT-NIST (C/N) efficiency tracing method
CIEMAT/NIST (C/N) method, developed by Centro de Investigationes Energéticas, Medioambientales y Tecnologicas (CIEMAT), Spain and the National Institute of Standards and Technology (NIST), U.S. is used for standardization of radionuclides with Liquid Scintillation (LS) Spectrometry by calculating the counting efficiency of the radionuclide to be assayed and using H-3 as a tracer . C/N program is suitable used for the calculation of the efficiency of nuclides decayed by β, β-γ, EC, EC-γ and nuclides with mixed decay . The basic principle of C/N LS efficiency tracing method is a combination of a theoretical calculation of the counting efficiency and an experimental determination of correction factors in three steps [61,64]:
Count rates (cpm) and the quench-indicating parameters (QIPs, i.e. tSIE) are determined for a set of samples of the nuclide to be measured, and for a set of H-3 standard samples, with a different quench. The tSIE values were calculated using the Ba-133 source inside of the instrument. By combining these data, a corresponding H-3 efficiency is obtained for each sample of the nuclide.
The universal curve of Figure of Merit (FOM) as a function of tSIE was plotted. The efficiency of the nuclide is theoretically calculated as a function of the efficiency of the tracer nuclide H-3.
This relation is used in conjunction with the measured data to calculate the efficiency for the nuclide and an activity value in dpm for each single measurement.
The parameters of emitters in different decay modes used for the C/N calculations are summarized as follows :
Pure β emitters (Sr-89, Sr-90, Y-90, and K-40): atomic number Z of the radionuclide, the mass number A, the endpoint energy EMax, and the shape parameters.
Pure γ emitters (Nb-93m): the efficiency is nearly 100%.
β+γ emitters, if the radionuclide has significant levels with half-lives in the order of the coincidence resolving time or the dead time of the equipment, a C/N calculation is not possible.
Pure EC emitters: the input parameters are the capture probabilities, PK; PL; PM, and the atomic parameters for the rearrangement: the fluorescence yields ωK and ωL (averaged), the probabilities of the X-rays (PKL, PKX, and PLX) and their average energies (EKL, EKX, and ELX), the emission probabilities of the Auger electrons (PKLL, PKLX, PKXY, and PLXY) and their average energies (EKLL, EKLX, EKXY, and ELXY).
EC+γ emitters (Co-57, Se-75, Sr-85, and Ba-133): the calculation method is the same as for β+γ nuclides.
The efficiency of LSC systems with respect to alpha radiation is in each case very close to unity. A tracer method is not necessary.
(c) The non-extrapolation tracer method
An alternative called “non-extrapolation tracer method” was proposed by Steyn et al. in 1979, where Fe-55 was used as a tracer to establish the figure-of-merit (FOM) of the detection system for the calculation of counting efficiency . The liquid scintillation method, for the determination of absolute activity of Mn-54 and Zn-65 from 4π(LS)e-γ data by direct calculation without efficiency extrapolation was performed. The non-extrapolation LS method relies on determining the probability of the γ-ray interacting with the scintillator solution, is described and validated by measurements made on Co-60 .
(d) The coincidence method by a 4πβ-γ system
Coincidence method comes from the additional coincidence channel, which records a disintegration event when it is detected in both β- and γ-channels. Typically, the system for absolute standardization is usually consisted of a gas-flow or pressurized proportional counter with 4π geometry as the α, β, electrons or X-ray detector and coupled to a pair of NaI(Tl) scintillation counters or a semiconductor detector, as γ detectors. The 4πβ-γ coincidence technique has been considered a primary standardization method due to its high accuracy and because it can obtain the radionuclide activity depending only on observables quantities [57,67].
Alternatively, solid or liquid scintillation counters (LSC) are used in place of gas-flow proportional counters. Advantages of using LSC counting in the 4π channel are that self-absorption does not occur, leading to Auger electrons being detected with relatively high efficiency; source preparation is easy; and the source geometry is highly reproducible. The latter leads to good reproducibility of the counting efficiency of the X-rays and Auger electrons, which in turn gives rise to consistent results amongst the counting sources. The efficiency data can generally be fitted with a linear function, particularly in the high-efficiency region, or by a low-order polynomial expression, giving rise to reliable extrapolated activity values .
Several examples for the applications of the coincidence method by a 4πβ-γ system are such as standardization of Ho-166m using the normal gas flow 4πβ-γ coincidence method , standardization of Tl-204 using Cs-134 as tracer and a 4πβ-γ coincidence system was used for the calibration , directly measured of radionuclides with EC decay schemes, e.g. I-125, Ir-192, Zn-65, and Ce-139 by a LS coincidence extrapolation technique , and standardization of Fe-55 using a “dual-tracers” method coupled with a 4πβ-γ coincidence calibration system .
(e) The triple to double coincidence ratio (TDCR) method
The TDCR method was first developed at the R.C., Poland and at the LNHB, France. The equipment consists in a detection unit, provided with three photomultipliers (PMs), acted by the light emitted in the vial containing the radioactive solution dissolved in a liquid scintillator, and the electronic unit . TDCR, allowing the observation of three kind of double coincidences (2-photodetectors) and triple coincidence (3-photodetectors) method in LSC, is a fundamental measurement method suitable to the standardization of pure-beta emitters, i.e. H-3, C-14, P-32, Ni-63, Tc-99, Tl-204 and some low energy electron-capture emitters, i.e. Fe-55 [59,60,70,71]. Detection efficiency variation can be achieved using techniques of chemical quenching, coaxial grey filters and PM tubes defocusing. The two former processes reduce the mean quantity of light emitted and the later reduces the detection probability . Basically, the specific experimental parameter (K) is equal to the ratio of the triple coincidences counting rate (NT) to the sum of double coincidences counting rate (ND). Determination of a counting efficiency (εD) for each counting point (ND) leads to the activity of the source (N0). The efficiency functions εT and εD are nonlinear functions for a particular emitter and counting system .
Two innovative TDCR instrumentations were developed:
The TDCR method of LSC is well established for measuring the activity of pure beta emitting and electron capture radionuclides. Recently, a new TDCR counting system was designed by the National Physical Laboratory (NPL) for activity assays of low-energy, pure β-emitting radionuclides and EC nuclides. Three photomultiplier tubes (PMT) were arranged in the optical chamber as well as a NaI(Tl) detector was mounted below the optical chamber. The detector allows 4πβ-γ coincidence measurements to be performed in parallel .
Radionuclides such as P-32, Sr-89, Y-90, Tl-204, and Rh-106 were successfully studied using an in-house built new TDCR-Čerenkov counter developed by Kossert. Since Čerenkov counting acts as natural discrimination for αemitters and low-energy β emitters, some potential radioactive impurities or progenies will not disturb the measurements. Two standard sources, e.g. Cl-36 and P-32 were used to determine the free parameter and to calculate the Čerenkov counting efficiencies. Since Čerenkov counting is more sensitive to changes in the computed β spectra, the method was extensively used to investigate β shape factor functions .
(f) The 4πγ counting method.
An ionization chamber system referring to a long living and stable standard source is very adequate for the comparison of γ-ray emitting radio-nuclides. In most cases Ra-226 sealed sources have been used as the reference because the Ra-226 sources were widely used in radiotherapy . Zimmerman et al. standardized and compared solution of Sn-117m by 4πβ liquid scintillation (LS) spectrometry and 4π γ-ray spectrometry (NaI(Tl) and high-purity germanium detectors). Massic activities were measured for determining the dose calibrator factor settings .
3.1.2. Uncertainty of measurement
Examples for the evaluation of detection efficiency (ε), activity accuracy, and measurement uncertainty (U) of absolute activity of radiopharmaceuicals and related radioisotopes are shown in Table 2. Components of combined uncertainty were further summarized in this section.
(a) Uncertainty for the efficiency tracing (and extrapolation) method using a non-H-3 standard solution
Components of combined uncertainty in the activity determination include counting statistics, background, dead time, weighing, decay scheme parameter, half-life, and extrapolation of efficiency curve . Source of uncertainty evaluated by Woods et al. in the absolute standardization of low energy β emitter, i.e. Pb-210 are counting, background, half life, β dead time, γ dead time, resolving times, choice of fit, count rate dependence, dead time formula, weighing, separation time, extrapolation range, contaminants, and reproducibility .
(b) Uncertainty for the C/N efficiency tracing method
Component of uncertainty in the standardization of Re-186 by the C/N method of LS efficiency tracing with H-3 include source preparation, scintillator stability, dead time, liquid-scintillation measurements, uncertainty due to H-3 reference standard, EC/β- branching ratio, spectral distributions for EC and β- branches. 
The contributions to the uncertainty of the value of the specific activity are volatility of H2 [GeCl6] during the preparation of solid sources for coincidence measurements, drop masses, counting statistics, background variation, accidental coincidences and dead time losses, Compton continuum of the 1077 keV peak included in the γ window around the 511 keV peak, decay scheme correct ion factor, correction factor for non-vanishing εEC, impurities and half-life uncertainty, and detection of 511 keV quanta in the β detector due to its γ sensitivity .
The components contributing to the uncertainty of 4πβ-γ coincidence method were estimated as follows: counting statistics and background variation, instrumental corrections, impurities, half-life uncertainty, decay scheme correction factor, and mass of droplet. Standard deviation of LSC composed of the following contributions: counting statistics, background variation, scintillator stability, comparison with H-3 tracer, instrumental corrections (dead time), dilution factor, droplet mass, radioactive impurities, half-life uncertainty, main decay data, uncertainty of the ε calculation due to the K-L model, capture probabilities PK, PL, fluorescence yields, ωK, ωL, spectral distribution of β particles, and average energy of weak Auger electrons .
Source of the uncertainty: counting statistics, mass, dead time, background, timing, chemical effects (adsorption, sample spread, impurities), input parameters and statistical model, quenching, kB influence, decay scheme parameters, and pulse shape discriminator setting. 
(c) Uncertainty for the non-extrapolation tracer method
The quoted total uncertainty (1σ) of 0.85% comprised mainly the components due to counting statistics (0.28%), afterpulsing (0.40%) and the evaluated decay-scheme data (0.63%). εM: double tube detection efficiency of Mn-54, εM*: reduced Mn-54 efficiency due to quenching caused by the addition of the Fe-55 aliquot .
(d) Uncertainty for the coincidence method by a 4πβ-γ system
Uncertainty components assayed by Koskinas et al. for the standardization of Eu-152 were counting statistics, weighing, dead time, impurities, half life, extrapolation of efficiency curve .
(e) Uncertainty for the TDCR method
The main source of uncertainty of TDCR method comes from the model describing the non-linearity of the scintillator due to the ionization quenching phenomenon . Type A standard uncertainty, i.e. counting statistics and type B standard uncertainty, i.e. extrapolation (interception uncertainty), spurious pulses, nonuniformity of sources, tracer activity, E. C. correction, dead-time, background, half-life, weighing were evaluated by Sahagia et al. .
(f) Uncertainty for the 4πγ counting method.
Construction of an ionization chamber efficiency curve is not a straightforward process as the curve has to be extracted from experimental calibration points analytically. The efficiency curve is implicitly contained in individual radionuclide coefficients and these are obtained experimentally or by Monte Carlo modelling or calculated back from the efficiency curve. Due to this variety, the interpretation and intercomparison of different efficiency curves is often hard and transferring individual radionuclide calibration coefficients between ionization chambers of different constructions is not a simple process .
3.1.3. International measurement program
One of the most important components in the quality system of radiopharmaceuticals is to establish the measurement traceability to international standards for ensuring the accurate and consistent of measurement results . Traceability of activity measurements is the critical part in the production and use of unsealed radioactive sources in nuclear medicine. The U.S. Nuclear Regulatory Commission (NRC) defines a medical event as a patient receiving an injected activity greater than 20% different from the prescribed dosage. Tthe Society of Nuclear Medicine (SNM) guidelines also recommend that the measurement be with 10% of the prescribed dosage. Moreover, the instruments being used are capable of accurate measurements to within 5% . Therefore, programs for the establishment and dissemination of activity measurement standards in nuclear medicine are held in many countries.
International comparison of standard sources and solutions, such as P-32, Mn-54, Zn-65, Ir-192, Tl-204, and Am-241, which is organized by the International Committee of Weights and Measures (CIPM), the EUROMET system, the former COMECOM, and bilateral comparisons, has been held since 1962 .
South Africa’s national radioactivity measurement standard is maintained by the National Metrology Laboratory (NML) of the Council for Scientific and Industrial Research (CSIR). Standardizations are undertaken by a number of direct methods utilizing liquid scintillation counting (LSC) .
Comparisons of activity measurements for I-131, Tl-201 and Tc-99m with radionuclide calibrators were organized in Cuba since 2002. During 2002, the Radionuclide Metrology Department of the Isotope Center (CENTIS-DMR) has organized several comparisons with various radionuclides in order to obtain information on the quality of the activity measurements during production and administration of radiopharmaceuticals in Cuba .
The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) conducts a series of Radiopharmaceutical Quality Assurance Test Program under a Memorandum of Understanding (MOU) between ARPANSA and the Therapeutic Goods Administration (TGA). For example, in 2005, 46 batches of 24 different types of radiopharmaceuticals, e.g., ready to use radiopharmaceuticals and kits for the preparation of Tc-99m were tested. Two percent in 46 batches of radiopharmaceuticals tested was failure to meet full specifications .
International comparison program of national metrological institutes for the standardization of Fe-55, which is a suitable radionuclide standard for X-ray spectrometers, was held by the Comité Consultative pour les Etalons de Mesures des Rayonnements Ionisants (CCEMRI) of the Bureau International des Poids et Mesures (BIPM) . National Metrology Institute of Japan - Advanced Industrial Science and Technology (NMIJ/AIST, Japan) and National Institute of Ionizing Radiation Metrology (ENEA-INMRI, Italy) have been involved in recent years, particularly those relevant in the frame of the international cooperation coordinated by the BIPM and the International Committee for Radionuclide Metrology (ICRM). Particular research activities are devoted on the field of the nuclear safety, nuclear medicine and environmental radionuclide measurements. . International comparisons held by BIPM also can be traced by laboratories such as National Institute for Physics and Nuclear Engineering (Romania) , Laboratorio de Metrologia Nuclear (Brazil) in collaboration with the Laboratório Nacional de Metrologia das Radiações Ionizantes, from Rio de Janeiro , Radiation Safety Systems Division, Bhabha Atomic Research Centre (India) , and Electrotechnical Laboratory (ETL) (Japan) .
The Ce-139 measurements formed part of a regional comparison organized by the Asia Pacific Metrology Programme (APMP) .
The National Institute of Standards and Technology (NIST) maintains a program for the establishment and dissemination of activity measurement standards in nuclear medicine, i.e. Ga-67, Y-90, Tc-99m, Mo-99, In-111, I-125, I-131, and Tl-201 for more than ten years. These standards are disseminated through Standard Reference Materials (SRMs), Calibration Services, radionuclide calibrator settings, and the NIST Radioactivity Measurement Assurance Program (NRMAP, formerly the NEI/NIST MAP). For over 3600 comparisons, 96% of the participants’ results differed from that of NIST by less than 10%, with 98% being less than 20%. The percentage of participants results within 10% of NIST ranges from 88% to 98% .
Measurements from a variety of types of detectors including, ionization chambers, radionuclide calibrators, solid state detectors, Ge detectors, NaI(Tl) detectors, liquid scintillation counters (LSC), Cherenkov counting, and proportional counter are reported .
3.2. Nuclear medicine imaging
3.2.1. PET, CT, PET/CT, and SPECT imaging
PET, CT, PET/CT, and SPECT are non-invasive imaging tools and applied for creating two dimensional (2D) cross section images of three dimensional (3D) objects. PET and SPECT can potentially provide functional or biochemical information by measuring distribution and kinetics of radiolabelled molecules, whereas CT visualizes X-ray density in tissues in the body. The PET imaging in oncology has been migrating from the use of dedicated PET scanners to the use of PET/CT tomographs. This is due to the advantages that PET/CT offers over dedicated PET. One of these advantages is that the integration of PET and CT imaging into a single scanning session allows excellent fusion of the acquired data. Although these nuclear medicine imaging tools provide many advantages and applications in diagnosing diseases clinically, they also poses some challenges and induce artifacts and quantitative errors that can affect the image quality.
3.2.2. Risks of artifact in PET, CT, and SPECT imaging
Artifacts and pitfalls can arise at any stage in the process of nuclear medicine imaging and can be grouped into issues related to the (i) patient, (ii) the equipment, or the technologist.
(a) Patient-related risks:
In PET/CT, the patient-related artifacts commonly found are due to metallic implants, truncation, and respiratory motion (or patient motion). These artifacts occur because the CT scan is used to replace a PET transmission scan for the purpose of attenuation correction of the PET data.
Metallic implants, such as dental fillings, hip prosthetics, or chemotherapy ports, cause high CT numbers and generate streaking artifacts on CT images due to their high photon absorption [85,86]. This increase CT numbers causes correspondingly high PET attenuation coefficients, resulting in an overestimation of the PET activity and thereby to a false-positive PET finding.
In PET/CT, truncation artifacts occur due to the difference in size of the field of view between the CT (50 cm) and PET (70 cm) tomographs [87,88] and frequently seen in large patients or patients scanned with arms down, such as in the case of melanoma and head and neck indications. When a patient extends beyond the CT field of view, the extended part of the anatomy is truncated and consequently is not represented in the reconstructed CT image. Truncation also causes streaking artifacts at the edge of the CT image, leading to an overestimation of the attenuation coefficients used to correct the PET data. This increase in attenuation coefficients creates a rim of high activity at the truncation edge, resulting in the misinterpretation of the PET scan.
The most prevalent artifact in PET/CT imaging is respiratory motion during scanning. The artifact is due to the discrepancy between the chest position on the CT image and the chest position on the PET image. PET images are acquired over time periods (time frames) that can vary from a few seconds to tens of minutes. Therefore, during such time periods various motions may have significant effects on the PET images. Both respiratory and contraction induced heart motions have major effect (source of error) on PET imaging of cardiac and thoracic regions. Some equipment, e.g., dose calibrators for the measurements of quantitative measurements is calibrated against or traceable to a reference source of whole body tomographs . Because of the long acquisition time of a PET scan, it is acquired while the patient is freely breathing. The final image is hence an average of many breathing cycles. On the other hand, a CT scan is usually acquired during a specific stage of the breathing cycle. This difference in respiratory motion between PET scans and CT scans results in breathing artifacts on PET/CT images. Several literatures have described this problem [90-91]. The artifacts resulted from respiratory motion or patient motion is also commonly found in myocardial perfusion SPECT. This is because that SPECT requires that the object of interest remains constant for the duration of the acquisition [92-93]. Visually detectable patient motion has been reported in 36% of clinical studies in one study  and 43% in another .
Source of clinical problems of the patients were also indicated by Hladik III, including (i) special patient populations, e.g., pregnant or breast-feeding women, pediatric and geriatric patients, patients requiring dialysis, incontinent, catheterized or miscellaneous patients, (ii) insufficient patient care, education, and preparation, e.g. insufficient patient instruction, shielding or protection in exposure and contamination problems, pregnancy testing, withholding xanthine-containing foods and drug-drug interaction prior to imaging, delay in the administration or imaging, metal implants of patient, (iii) improper behavior of patient, e.g., excessive movement, contamination from incontinence, attenuation from jewelry, prostheses, or implants, etc., and (iv) unexpected altered biodistributions may be undetectable, adverse reactions or untoward effects, 
(b) Equipment- or technologist-related risks:
There are several patient-related artifacts and interpretation pitfalls that can potentially compromise nuclear medicine imaging, as discussed above. In order to minimize or identify these artifacts, technologists play an important role in recognizing and correcting them. For example, technologists should ask patients to remove all metallic objects before imaging and should document the location of non-removable metallic objects to minimize or identify the artifacts from metallic implants. In PET/CT imaging, it is crucial for technologists to carefully position patients at the center of the field of view and with arms above head to reduce truncation artifacts. Moreover, in order to minimize the artifacts from respiratory motion and produce accurately quantifiable images, it is also essential that technologists instruct patients about breath-hold techniques before the scanning session.
Moreover, sources of clinical problems of error medication also include fail of (i) patient identification, (ii) dosage prescription and administration, (iii) radionuclide administration, (iv) radiopharmaceutical prescription and administration in kinetics or finished product purity testing, (v) interventional medications, (vi) injection technique, (vii) radiopharmaceutical labelled, (viii) preparation or execution of diagnostic or therapeutic procedure, and (ix) radiation protection [7,96].
QC performed on nuclear medicine cameras provides the confidence to technologists and physicians that a scan supplies an accurate representation of the radioisotope distribution in the patient. The instrumentation for nuclear medicine imaging is more complex than that used for whole-body and planar imaging, and requires careful quality control to ensure optimum performance. According to the standards, the main performance parameters are divided into two groups. The first group includes basic intrinsic measurements: spatial resolution in axial and transaxial directions, sensitivity, count rate capabilities by measuring the system dead time and the generation of random events at different radioactivity levels, and scatter fraction of γ rays emitted by the annihilation of positron. The second group includes measurements of the accuracy of corrections for physical effects, specifically: uniformity correction, scatter correction, attenuation correction, and count rate linearity correction. Other possible tests to be added to the list of acceptance or performance tests such as: noise equivalent count rate, partial volume and spillover, motion artefacts, image quality test, and PET/CT image co-registration .
Nuclear medicine imaging increases the accuracy of diagnosis by combining anatomic information with functional imaging. It is highly dependent on a host of technical considerations. Knowledgeable technologists can minimize or reduce artifacts and other potential problems with image acquisition and, in that way, produce better-quality images.