First-in-Man Evaluation of 2 High-Affinity PSMA-Avid Small Molecules for Imaging Prostate Cancer

This phase 1 study was performed to determine the pharmacokinetics and ability to visualize prostate cancer in bone, soft-tissue, and the prostate gland using I-123-MIP-1072 and I-123-MIP-1095, novel radiolabeled small molecules targeting prostate-specific membrane antigen. Methods: Seven patients with a documented history of prostate cancer by histopathology or radiologic evidence of metastatic disease were intravenously administered 370 MBq (10 mCi) of I-123-MIP-1072 and I-123-MIP-1095 2 wk apart in a crossover trial design. I-123-MIP-1072 was also studied in 6 healthy volunteers. Whole-body planar and SPECT/CT imaging was performed and pharmacokinetics studied over 2-3 d. Target-to-background ratios were calculated. Absorbed radiation doses were estimated using OLINDA/EXM. Results: I-123-MIP-1072 and I-123-MIP-1095 visualized lesions in soft tissue, bone, and the prostate gland within 0.5-1 h after injection, with retention beyond 48 h. Target-to-background ratios from planar images averaged 2:1 at 1 h, 3:1 at 4-24 h, and greater than 10:1 at 4 and 24 h for SPECT/CT. Both agents cleared the blood in a biphasic manner; clearance of I-123-MIP-1072 was approximately 5 times faster. I-123-MIP-1072 was excreted in the urine, with 54% and 74% present by 24 and 72 h, respectively. In contrast, only 7% and 20% of I-123-MIP-1095 had been renally excreted by 24 and 72 h, respectively. Estimated absorbed radiation doses were 0.054 versus 0.110 mGy/MBq for the kidneys and 0.024 versus 0.058 mGy/MBq for the liver, for I-123-MIP-1072 and I-123-MIP-1095, respectively. Conclusion: I-123-MIP-1072 and I-123-MIP-1095 detect lesions in soft tissue, bone, and the prostate gland at as early as 1-4 h. These novel radiolabeled small molecules have excellent pharmacokinetic and pharmacodynamic profiles and warrant further development as diagnostic and potentially when labeled with I-131 therapeutic radiopharmaceuticals.