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Theragnostic pairs of isotopes are used to infer radiation dosimetry for a therapeutic radiopharmaceutical from a diagnostic imaging study with the same tracer molecule labelled with an isotope better suited for the imaging task. We describe the transfer of radiation dosimetry from the diagnostic radioiodine isotope 123 I, labelled for the hypoxia tracer molecule iodoazomycin arabinoside ([ 123 I]IAZA), to isotopes 131 I (therapeutic) and 124 I (PET imaging). Uncertainties introduced by the dissimilar isotope half-lives are discussed in detail. Radioisotope dosimetries for [ 123 I]IAZA were obtained previously. These data are used here to calculate residence times for 131 I and 124 I and their uncertainties. We distinguish two cases when extrapolating to infinity: purely physical decay (case A) and physical decay plus biological washout (case B). Organ doses were calculated using the MIRD schema with the OLIDNA/EXM code. Significant increases in some organ doses (in mSv per injected activity) were found for 131 I and 124 I. The most affected organs were the intestinal walls, thyroid, and urinary bladder wall. Uncertainty remained similar to 123 I for case A but considerably greater for case B, especially for long biological half-lives (GI tract). Normal tissue dosimetries for IAZA must be considered carefully when substituting isotope species. A long biological half-life can significantly increase dosimetric uncertainties. These findings are relevant when considering PET imaging studies with [ 124 I]IAZA or therapeutic administration of [ 131 I]IAZA.

In 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) studies, maximum standardized uptake value (SUV max ) is the parameter commonly used to provide a measurement of the metabolic activity of a tumor. SUV normalized by body mass is affected by the proportions of body fat and lean tissue, which present high variability in patients with cancer. SUV corrected by lean body mass (LBM), denoted as SUL, is recommended to provide more accurate, consistent, and reproducible SUV results; however, LBM is frequently estimated rather than measured. Given the increasing importance of a quantitative PET parameter, especially when comparing PET studies over time to evaluate disease response clinically, and its use in oncological clinical trials, we set out to evaluate the commonly used equations originally derived by James (1976) and Janmahasatian et al. (2005) against computerized tomography (CT)-derived measures of LBM., Methods: Whole-body 18 F-FDG PET images of 195 adult patients with cancer were analyzed retrospectively. Representative liver SUV mean was normalized by total body mass. SUL was calculated using a quantitative determination of LBM based on the CT component of the PET/CT study (LBM CT ) and compared against the equation-estimated SUL. Bland and Altman plots were generated for SUV-SUL differences., Results: This consecutive sample of patients undergoing usual care (men, n = 96; women, n = 99) varied in body mass (38-127 kg) and in Body Mass Index (BMI) (14.7-47.2 kg/m2). LBM CT weakly correlated with body mass (men, r 2 = 0.32; women, r 2 = 0.22), and thus SUV and SUL CT were also weakly correlated (men, r 2 = 0.24; women, r 2 = 0.11). Equations proved inadequate for the assessment of LBM. LBM estimated by James' equation showed a mean bias (overestimation of LBM compared with LBM CT ) in men (+6.13 kg; 95% CI 4.61-7.65) and in women (+6.32 kg; 95% CI 5.26-7.39). Janmahasatian's equation provided similarly poor performance., Conclusions: CT-based LBM determinations incorporate the patient's current body composition at the time of a PET/CT study, and the information garnered can provide care teams with information with which to more accurately determine FDG uptake values, allowing comparability over multiple scans and treatment courses and will provide a robust basis for the use of PET Response Criteria in Solid Tumors (PERCIST) in clinical trials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Riauka, Baracos, Reif, Juengling, Robinson, Wieler and McEwan.)

Objective: The purpose of this study was to assess the efficacy of Lu-labeled peptide receptor radionuclide therapy (PRRT) induction treatments for patients with unresectable metastatic neuroendocrine tumors., Methods: MEDLINE, EMBASE, and Ovid were systematically searched with keywords "lutetium," "Lu-177," "PRRT," "neuroendocrine," and "prognosis." Studies evaluating treatment with Lu-labeled PRRT were assessed for disease response and/or disease control rate by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 or 1.1, modified RECIST, Southwest Oncology Group (SWOG), or modified SWOG criteria. Pooled proportions of disease response and control rates were calculated for both fixed- and random-effects models., Results: Eighteen studies with 1920 patients were included (11 with 1268 patients using RECIST and 6 with 804 patients using SWOG). By RECIST criteria, the pooled disease response rate by random-effects model was 29.1% (95% confidence interval [CI], 20.2%-38.9%), and disease control rate was 74.1% (95% CI, 67.8%-80.0%). By SWOG criteria, the pooled disease response rate by random-effects model was 30.6% (95% CI, 20.7%-41.5%), and disease control rate was 81.1% (95% CI, 76.4%-85.4%)., Conclusions: Induction therapy, typically 4 treatments, with Lu PRRT is an effective method of treating unresectable metastatic neuroendocrine tumors with significant disease response and control rates.

This paper presents the irradiation and processing of high-current 100 Mo targets at the University of Alberta (UofA) in a GMP compliant setting. For purpose of comparison with a second production facility, additional studies at Centre Hospitalier Universitaire de Sherbrooke (CHUS) are also described., Introduction: More than 70% of today's diagnostic radiopharmaceuticals are based on 99m Tc, however the conventional supply chain for obtaining 99m Tc is fragile. The aim of this work was to demonstrate reliable high yield production and processing of 99m Tc with medium-energy, high-current, cyclotrons., Methods: We used two cyclotrons (TR-24, Advanced Cyclotron Systems, Inc) for irradiations with 22 MeV or 24 MeV incident energy and 400 μA current up to a maximum of 6 h. The irradiated 100 Mo was dissolved using peroxide, basified using ammonium carbonate, and purified using a PEG-based solid phase extraction technique., Results: High-yield productions with 22 MeV (400 μA, 6 h) yielded an average isolated [ 99m Tc]TcO 4 - yield of 878 GBq ± 99 GBq (23.7 Ci ± 2.7 Ci) decay corrected to EOB, n = 8 (isolated saturation yield: 4.36 ± 0.49 GBq/μA). Irradiations with 24 MeV (400 μA, 6 h) resulted in an average isolated [ 99m Tc]TcO 4 - yield of 993 GBq ± 100 GBq (26.8 Ci ± 2.7 Ci) decay corrected to EOB, n = 7 (isolated saturation yield: 4.97 ± 0.50 GBq/μA). These yields corresponds to 600-700 GBq (16-19 Ci) of [ 99m Tc]TcO 4 - at release (i.e. 3 hour post-EOB). For all tested batches, the QC results were within the recently published specifications in the European Pharmacopoeia., Conclusion: Reliable near-TBq production yields for 99m Tc can be obtained using medium-energy cyclotrons., Advances in Knowledge and Implications for Patient Care: This work presents evidence that medium-energy high-current cyclotrons can provide high yields of [ 99m Tc]TcO 4 - with radionuclidic impurities levels within the specifications of the existing European Pharmacopoeia monograph, indicating that this technology can have a share in the future 99m Tc supply market., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The objective of this work is to evaluate the potential effect of cardiac stress exercise on the accumulation of [ 123 I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise normal myocardium in healthy volunteers, and to determine the impact of exercise on [ 123 I]IAZA pharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies of focal myocardial hypoxia in cardiac patients using [ 123 I]IAZA. Three healthy male volunteers ran the 'Bruce' treadmill protocol, a clinically-accepted protocol designed to expose myocardial ischemia in patients. The 'Bruce' criterion heart rate is 85% of [220-age]. Approximately one minute before reaching this level, [ 123 I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1-3 min) single intravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for an additional 1 min before being transferred to a gamma camera. Serum samples were collected from the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h post injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for [ 123 I]IAZA and total radioactivity (total[ 123 I]) using compartmental and noncompartmental analyses. Whole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and scintigraphic images were compared to previously published [ 123 I]IAZA data from healthy volunteers rest. Following exercise stress, both [ 123 I]IAZA and total[ 123 I] exhibited bi-exponential decline profiles, with rapid distribution phases [half-lives (t 1/2α ) of 1.2 and 1.4 min, respectively], followed by slower elimination phases [t 1/2β of 195 and 290 min, respectively]. Total body clearance (CL TB ) and the steady state volume of distribution (V ss ) were 0.647 L/kg and 185 mL/min, respectively, for [ 123 I]IAZA and 0.785 L/kg and 135 mL/min, respectively, for total[ 123 I]. The t 1/2β , CL TB and V ss values were comparable to those reported previously for rested volunteers. The t 1/2α was approximately 4-fold shorter for [ 123 I]IAZA and approximately 3-fold shorter for total[ 123 I] under exercise relative to rested subjects. The heart region was visualized in early whole body scintigraphic images, but later images showed no accumulated radioactivity in this region, and no differences from images reported for rested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle was consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [ 123 I]IAZA in exercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers. There was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium, supporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable myocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t 1/2α was shortened, reflecting increased cardiac output associated with exercise. It is concluded that because [ 123 I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency. [ 123 I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients undergoing stress-test-based diagnosis., Competing Interests: The authors declare no conflict of interest.

Purpose of the Study: To compare efficacy of thyroid remnant ablation using 30 mCi or 50 mCi 131-I in papillary thyroid cancer patients., Materials and Methods: Five hundred and fifteen consecutive patients with Tumor-Node-Metastasis (TNM) stages T1-T3 N1/N0/NX receiving either 30 mCi or 50 mCi I-131 were analyzed for the effectiveness of remnant ablation using rhTSH-stimulated serum thyroglobulin. One hundred and five consecutive patients receiving 100 mCi I-131 were analyzed for the incidence of radiation thyroiditis and sialadenitis., Results and Conclusions: Doses of 30 mCi and 50 mCi were equally effective for low- and moderate-risk disease but 30 mCi was less effective for T1T2NX disease, and 50 mCi was less effective for T3 compared to T1T2 disease. Low dose radiation hypersensitivity or unknown more extensive disease may have accounted for observed differences. Radiation thyroiditis and sialadenitis were more common in a comparison series of 100 mCi dose compared to 30 mCi, but not more common than in 50 mCi doses.

A single-site prospective open-label clinical study with cyclotron-produced sodium 99m Tc-pertechnetate ( 99m Tc-NaTcO 4 ) was performed in patients with indications for a thyroid scan to demonstrate the clinical safety and diagnostic efficacy of the drug and to confirm its equivalence with conventional 99m Tc-NaTcO 4 eluted from a generator. Methods: 99m Tc-NaTcO 4 was produced from enriched 100 Mo (99.815%) with a cyclotron (24 MeV; 2 h of irradiation) or supplied by a commercial manufacturer (bulk vial eluted from a generator). Eleven patients received 325 ± 29 (mean ± SD) MBq of the cyclotron-produced 99m Tc-NaTcO 4 , whereas the age- and sex-matched controls received a comparable amount of the generator-derived tracer. Whole-body and thyroid planar images were obtained for each participant. In addition to the standard-energy window (140.5 keV ± 7.5%), data were acquired in lower-energy (117 keV ± 10%) and higher-energy (170 keV ± 10%) windows. Vital signs and hematologic and biochemical parameters were monitored before and after tracer administration. Results: Cyclotron-produced 99m Tc-NaTcO 4 showed organ and whole-body distributions identical to those of conventional 99m Tc-NaTcO 4 and was well tolerated. All images led to a clear final diagnosis. The fact that the number of counts in the higher-energy window was significantly higher for cyclotron-produced 99m Tc-NaTcO 4 did not influence image quality in the standard-energy window. Image definition in the standard-energy window with cyclotron-produced 99m Tc was equivalent to that with generator-eluted 99m Tc and had no particular features allowing discrimination between the 99m Tc production methods. Conclusion: The systemic distribution, clinical safety, and imaging efficacy of cyclotron-produced 99m Tc-NaTcO 4 in humans provide supporting evidence for the use of this tracer as an equivalent for generator-eluted 99m Tc-NaTcO 4 in routine clinical practice., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose: A robust method is required to standardise objective reporting of diagnostic 123 I-mIBG images in neuroblastoma. Prerequisites for an appropriate system are low inter- and intra-observer error and reproducibility across a broad disease spectrum. We present a new reporting method, developed and tested for SIOPEN by an international expert panel., Method: Patterns of abnormal skeletal 123 I-mIBG uptake were defined and assigned numerical scores [0-6] based on disease extent within 12 body segments. Uptake intensity was excluded from the analysis. Data sets from 82 patients were scored independently by six experienced specialists as unblinded pairs (pre- and post-induction chemotherapy) and in random order as a blinded study. Response was defined as ≥50 % reduction in post induction score compared with baseline., Results: In total, 1968 image sets were reviewed individually. Response rates of 88 % and 82 % were recorded for patients with baseline skeletal scores ≤23 and 24-48 respectively, compared with 44 % response in patients with skeletal scores >48 (p = 0.02). Reducing the number of segments or extension scale had a small but statistically negative impact upon the number of responses detected. Intraclass correlation coefficients [ICCs] calculated for the unblinded and blinded study were 0.95 at diagnosis and 0.98 and 0.99 post-induction chemotherapy, respectively., Conclusions: The SIOPEN mIBG score method is reproducible across the full spectrum of disease in high risk neuroblastoma. Numerical assessment of skeletal disease extent avoids subjective evaluation of uptake intensity. This robust approach provides a reliable means with which to examine the role of 123I mIBG scintigraphy as a prognostic indicator in neuroblastoma., Competing Interests: Compliance with ethical standards All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors. Informed consent Informed consent was obtained from all individual participants or legitimate representatives included in the study. Funding Charity Adam’s Hats supported the pilot study. The trial RDE database was supported by grants provided by Amgen International and Amgen UK. EC grant QLRI-CT-2002-01768 for the SIOPEN-R-NET project supporting national and international data management. Conflict of interest Lewington V declares that she has no conflict of interest. Poetschger U declares that she has no conflict of interest. Lambert B declares that she has no conflict of interest. Bar Sever Z declares that he has no conflict of interest. Castellani MR declares that she has no conflict of interest. Lynch T declares that he has no conflict of interest. Giammarile F declares that he has no conflict of interest. McEwan AJB declares that he has no conflict of interest. Shulkin B declares that he has no conflict of interest. Staudenherz A declares that he has no conflict of interest. Mario Drobics declares that he has no conflict of interest. Ladenstein R declares that she has no conflict of interest.

Hydrophobic adsorbents such as C18 and C30 were coated with PEG and subsequently used for the separation of Mo/Tc. The most effective resin for adsorbing PEG was the C18-U resin, which demonstrated a coating capacity of 97.6±2.8mg PEG per g of resin. The ability to adsorb pertechnetate was proportional to the amount of PEG coated on the hydrophobic resin. The [(99m)Tc]pertechnetate recovery during the separation of cyclotron produced (99m)Tc from (100)Mo was 91.8±0.3% (n=2). The resultant product met relevant USP monograph specifications., (Copyright © 2016 Elsevier Ltd. All rights reserved.)