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para- Aminobenzoic acid (PABA) has been previously used as an exogenous marker to verify completion of 24-h urine sampling. Therefore, we hypothesized that PABA radiolabeled with 11 C might allow high-quality dynamic PET of the kidneys with less radiation exposure than other agents because of its shorter biologic and physical half-life. We evaluated if 11 C-PABA can visualize renal anatomy and quantify function in healthy rats and rabbits and in a first-in-humans study on healthy volunteers. Methods: Healthy rats and rabbits were injected with 11 C-PABA intravenously. Subsequently, dynamic PET was performed, followed by postmortem tissue-biodistribution studies. 11 C-PABA PET was directly compared with the current standard, 99m Tc-mercaptoacetyltriglycin, in rats. Three healthy human subjects also underwent dynamic PET after intravenous injection of 11 C-PABA. Results: In healthy rats and rabbits, dynamic PET demonstrated a rapid accumulation of 11 C-PABA in the renal cortex, followed by rapid excretion through the pelvicalyceal system. In humans, 11 C-PABA PET was safe and well tolerated. There were no adverse or clinically detectable pharmacologic effects in any subject. The cortex was delineated on PET, and the activity gradually transited to the medulla and then pelvis with high spatiotemporal resolution. Conclusion: 11 C-PABA demonstrated fast renal excretion with a very low background signal in animals and humans. These results suggest that 11 C-PABA might be used as a novel radiotracer for functional renal imaging, providing high-quality spatiotemporal images with low radiation exposure., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

5D3 is a new high-affinity murine monoclonal antibody specific for prostate-specific membrane antigen (PSMA). PSMA is a target for the imaging and therapy of prostate cancer. 111 In-labeled antibodies have been used as surrogates for 177 Lu/ 90 Y-labeled therapeutics. We characterized 111 In-DOTA-5D3 by SPECT/CT imaging, tissue biodistribution studies, and dosimetry. Methods: Radiolabeling, stability, cell uptake, and internalization of 111 In-DOTA-5D3 were performed by established techniques. Biodistribution and SPECT imaging were done on male nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice bearing human PSMA(+) PC3 PIP and PSMA(-) PC3 flu prostate cancer xenografts on the upper right and left flanks, respectively, at 2, 24, 48, 72, and 192 h after injection. Biodistribution was also evaluated in tumor-free, healthy male CD-1 mice. Blocking studies were performed by coinjection of a 10-fold and 50-fold excess of 5D3 followed by biodistribution at 24 h to determine PSMA binding specificity. The absorbed radiation doses were calculated on the basis of murine biodistribution data, which were translated to a human adult man using organ weights as implemented in OLINDA/EXM. Results: 111 In-DOTA-5D3 was synthesized with specific activity of approximately 2.24 ± 0.74 MBq/μg (60.54 ± 20 μCi/μg). Distribution of 111 In-DOTA-5D3 in PSMA(+) PC3 PIP tumor peaked at 24 h after injection and remained high until 72 h. Uptake in normal tissues, including the blood, spleen, liver, heart, and lungs, was highest at 2 h after injection. Coinjection of 111 In-DOTA-5D3 with a 10- and 50-fold excess of nonradiolabeled antibody significantly reduced PSMA(+) PC3 PIP tumor and salivary gland uptake at 24 h but did not reduce uptake in kidneys and lacrimal glands. Significant clearance of 111 In-DOTA-5D3 from all organs occurred at 192 h. The highest radiation dose was received by the liver (0.5 mGy/MBq), followed by the spleen and kidneys. Absorbed radiation doses to the salivary and lacrimal glands and bone marrow were low. Conclusion: 111 In-DOTA-5D3 is a new radiolabeled antibody for imaging and a surrogate for therapy of malignant tissues expressing PSMA., (© 2019 by the Society of Nuclear Medicine and Molecular Imaging.)

Whole-body PET/CT was performed using 124 I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. Methods: Healthy subjects aged 18-65 y underwent whole-body PET/CT either at 4, 24, and 48 h or at 24, 48, and 72 h after intravenous injection of 124 I-DPA-713. Time-activity curves were generated and used to calculate organ time-integrated activity coefficients for each subject. The resulting time-integrated activity coefficients provided input data for calculation of organ absorbed doses and effective dose for each subject using OLINDA. Subjects were genotyped for the TSPO polymorphism rs6971, and plasma protein binding of 124 I-DPA-713 was measured. Results: Three male and 3 female adults with a mean age of 40 ± 19 y were imaged. The mean administered activity and mass were 70.5 ± 5.1 MBq (range, 62.4-78.1 MBq) and 469 ± 34 ng (range, 416-520 ng), respectively. There were no adverse or clinically detectable pharmacologic effects in any of the 6 subjects. No changes in vital signs, laboratory values, or electrocardiograms were observed. 124 I-DPA-713 cleared rapidly (4 h after injection) from the lungs, with hepatic elimination and localization to the gastrointestinal tract. The mean effective dose over the 6 subjects was 0.459 ± 0.127 mSv/MBq, with the liver being the dose-limiting organ (0.924 ± 0.501 mGy/MBq). The percentage of free radiotracer in blood was approximately 30% at 30 and 60 min after injection. Conclusion: 124 I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

The data that have been used in almost all calculations of MIRD S value absorbed dose and effective dose are based on stylized anatomic computational phantoms and tissue-weighting factors adopted by the International Commission on Radiological Protection (ICRP) in its publication 60. The more anatomically realistic phantoms that have recently become available are likely to provide more accurate effective doses for diagnostic agents. 68 Ga-DOTATATE is a radiolabeled somatostatin analog that binds with high affinity to somatostatin receptors, which are overexpressed in neuroendocrine tumors and can be used for diagnostic PET/CT-based imaging. Several studies have reported effective doses for 68 Ga-DOTATATE using the stylized Cristy-Eckerman (CE) phantoms from 1987; here, we present effective dose calculations using both the ICRP 60 and more updated formalisms. Methods: Whole-body PET/CT scans were acquired for 16 patients after 68 Ga-DOTATATE administration. Contours were drawn on the CT images for spleen, liver, kidneys, adrenal glands, brain, heart, lungs, thyroid gland, salivary glands, testes, red marrow (L1-L5), muscle (right thigh), and whole body. Dosimetric calculations were based on the CE phantoms and the more recent ICRP 110 reference-voxel phantoms. Tissue-weighting factors from ICRP 60 and ICRP 103 were used in effective dose calculations for the CE phantoms and ICRP 110 phantoms, respectively. Results: The highest absorbed dose coefficients (absorbed dose per unit activity) were, in descending order, in the spleen, pituitary gland, kidneys, adrenal glands, and liver. For ICRP 110 phantoms with tissue-weighting factors from ICRP 103, the effective dose coefficient was 0.023 ± 0.003 mSv/MBq, which was significantly lower than the 0.027 ± 0.005 mSv/MBq calculated for CE phantoms with tissue-weighting factors from ICRP 60. One of the largest differences in estimated absorbed dose coefficients was for the urinary bladder wall, at 0.040 ± 0.011 mGy/MBq for ICRP 110 phantoms compared with 0.090 ± 0.032 mGy/MBq for CE phantoms. Conclusion: This study showed that the effective dose coefficient was slightly overestimated for CE phantoms, compared with ICRP 110 phantoms using the latest tissue-weighting factors from ICRP 103. The more detailed handling of electron transport in the latest phantom calculations gives significant differences in estimates of the absorbed dose to stem cells in the walled organs of the alimentary tract., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Patients with metastatic differentiated thyroid cancer (DTC) may be prepared using either thyroid-stimulating hormone withdrawal (THW) or recombinant human thyroid-stimulating hormone (rhTSH) injections before 131 I administration for treatment. The objective of this study was to compare the absorbed dose to the critical organs and tumors determined by 124 I PET/CT-based dosimetry for 131 I therapy of metastatic DTC when the same patient was prepared with and imaged after both THW and rhTSH injections. Methods: Four DTC patients at MedStar Washington Hospital Center were first prepared using the rhTSH method and imaged by 124 I PET/CT at 2, 24, 48, 72, and 96 h after administration of approximately 30-63 MBq of 124 I. After 5-8 wk, the same patients were prepared using the THW method and imaged as before. The 124 I PET/CT images acquired as part of a prospective study were used to perform retrospective dosimetric calculations for 131 I therapy for the normal organs with the dosimetry package 3D-RD. The absorbed doses from 131 I for the lungs, liver, heart, kidneys, and bone marrow were obtained for each study (rhTSH and THW). Twenty-two lesions in 3 patients were identified. The contours were drawn on each PET image of each study. Time-integrated activity coefficients were calculated and used as input in OLINDA/EXM sphere dose calculator to obtain the absorbed dose to tumors. Results: The THW-to-rhTSH organ absorbed dose ratio averaged over 5 organs for the first 3 patients was 1.5, 2.5, and 0.64, respectively, and averaged over 3 organs for the fourth patient was 1.1. The absorbed dose per unit administered activity to the bone marrow was 0.13, 0.086, 0.33, and 0.068 mGy/MBq after rhTSH and 0.11, 0.14, 0.22, and 0.080 mGy/MBq after THW for each patient, respectively. With the exception of 3 lesions of 1 patient, the absorbed dose per unit administered activity of 131 I was higher in the THW study than in the rhTSH study. The ratio of the average tumor absorbed dose after stimulation by THW compared with stimulation by rhTSH injections was 3.9, 27, and 1.4 for patient 1, patient 2, and patient 3, respectively. The ratio of mean tumor to bone marrow absorbed dose per unit administered activity of 131 I, after THW and rhTSH, was 232 and 62 (patient 1), 12 and 0.78 (patient 2), and 22 and 11 (patient 3), respectively. Conclusion: The results suggest a high patient variability in the overall absorbed dose to the normal organs per MBq of 131 I administered, between the 2 TSH stimulation methods. The tumor-to-dose-limiting-organ (bone marrow) absorbed dose ratio, that is, the therapeutic index, was higher in the THW-aided than rhTSH-aided administrations. Additional comparison for tumor and normal organ absorbed dose in patients prepared using both methods is needed before definitive conclusions may be drawn regarding rhTSH versus THW patient preparation methods for 131 I therapy of metastatic DTC., (© 2017 by the Society of Nuclear Medicine and Molecular Imaging.)