First-in-human imaging with 89Zr-Df-IAB2M Anti-PSMA minibody in patients with metastatic prostate cancer: Pharmacokinetics, biodistribution, dosimetry, and lesion uptake

Neeta Pandit-Taskar, Joseph A. O'Donoghue, Shutian Ruan, Serge K. Lyashchenko, Jorge A. Carrasquillo, Glenn Heller, Danny F. Martinez, Sarah M. Cheal, Jason S. Lewis, Martin Fleisher, Jennifer S. Keppler, Robert E. Reiter, Anna M. Wu, Wolfgang A. Weber, Howard I. Scher, Steven M. Larson, Michael J. Morris

Research output: Contribution to journalArticlepeer-review

108 Scopus citations

Abstract

We conducted a phase I dose-escalation study with 89Zr-desferrioxamine-IAB2M (89Zr-IAB2M), an anti-prostate-specific membrane antigen minibody, in patients with metastatic prostate cancer. Methods: Patients received 185 MBq (5 mCi) of 89Zr-IAB2M and Df-IAB2M at total mass doses of 10 (n = 6), 20 (n = 6), and 50 mg (n = 6). Wholebody 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 0.41mSv/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 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.

Original languageEnglish
Pages (from-to)1858-1864
Number of pages7
JournalJournal of Nuclear Medicine
Volume57
Issue number12
DOIs
StatePublished - 1 Dec 2016
Externally publishedYes

Keywords

  • 89Zr- IAB2M
  • Dosimetry
  • Minibody
  • PSMA
  • Prostate cancer imaging

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