Purpose Prostate-specific membrane antigen (PSMA) is a recognized target for imaging prostate cancer. Here we present initial safety, biodistribution, and radiation dosimetry results with [18F]DCFPyL, a second-generation fluorine-18-labeled small-molecule PSMA inhibitor, in patients with prostate cancer. Procedures Biodistribution was evaluated using sequential positron-emission tomography (PET) scans in nine patients with prostate cancer. Time-activity curves from the most avid tumor foci were determined. The radiation dose to selected organs was estimated using OLINDA/EXM. Results No major radiotracer-specific adverse events were observed. Physiologic accumulation was observed in known sites of PSMA expression. Accumulation in putative sites of prostate cancer was observed (SUVmax up to >100, and tumor-to-blood ratios up to >50). The effective radiation dose from [18F]DCFPyL was 0.0139 mGy/MBq or 5 mGy (0.5 rem) from an injected dose of 370 MBq (10 mCi). Conclusions [18F]DCFPyL is safe with biodistribution as expected, and its accumulation is high in presumed primary and metastatic foci. The radiation dose from [18F]DCFPyL is similar to that from other PET radiotracers.

Whole-body PET/CT was performed using I-DPA-713, a radioligand for the 18-kDa translocator protein (TSPO), to determine biodistribution and radiation dosimetry. 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 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 polymorphism rs6971, and plasma protein binding of I-DPA-713 was measured. 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. 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. I-DPA-713 clears rapidly from the lungs, with predominantly hepatic elimination, and is safe and well tolerated in healthy adults.

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 tumorto-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.

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(1) 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(1) 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(1) 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.