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

Abstract

Anti-prostate-specific membrane antigen (PSMA) imaging with minibodies has the advantage of faster clearance due to smaller size. We conducted a Phase I dose escalation study with ⁸⁹Zr-desferrioxamine-IAB2M (⁸⁹Zr-IAB2M), an anti-PSMA minibody, in patients with metastatic prostate cancer (mPC). Methods: Patients received 185 MBq (5 mCi) of ⁸⁹Zr-IAB2M and Df-IAB2M at total mass doses of 10 mg (n = 6), 20 mg (n = 6), and 50 mg (n = 6). Whole-body (WB) 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. WB clearance was monoexponential with median biological half (T1/2b) of 215 h, while serum clearance showed biexponential kinetics with a median T1/2b of 3.7 h (12.3 %/L) and 33.8 h (17.9 %/L). The RAD 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 ⁸⁹Zr-IAB2M, most visualized by 48 h imaging. Conclusion: ⁸⁹Zr-IAB2M is safe and demonstrates favorable biodistribution and kinetics for targeting mPC. Imaging with 10 mg minibody mass provides optimal biodistribution, and imaging at 48 h post-injection provides good lesion visualization. Assessment of lesion targeting is being studied in detail in an expansion cohort.