First-in-Human Imaging with 89Zr-Df-IAB2M Anti-PSMA Minibody in Patients with Metastatic Prostate Cancer: Pharmacokinetics, Biodistribution, Dosimetry, and Lesion Uptake

We conducted a phase I dose-escalation study with Zr-89-desferriox-amjne-IAB2M (Zr-89-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. Methods: Patients received 185 MBq (5 mCi) of Zr-89-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Whole body and serum clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated, and the effect of mass escalation was analyzed. Results: Eighteen patients were injected and scanned without side effects. Whole-body clearance was monoexponential, with a median biologic half-life of 215 h, whereas serum clearance showed biexponential kinetics, with a median biologic half-life of 3.7 (12.3%/L) and 33.8 h (17.9%/L). The radiation absorbed dose estimates were 1.67, 1.36, and 0.32 mGy/MBq to liver, kidney, and marrow, respectively, with an effective dose of 0.41 mSv/MBq (1.5 rem/mCi). Both skeletal and nodal lesions were detected with Zr-89-IAB2M, most visualized by 48-h imaging. Conclusion: Zr-89-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting metastatic prostate cancer. Imaging with 10 mg of minibody mass provides optimal biodistribution, and imaging at 48 h after injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.