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

J Nucl Med. 2016 Dec;57(12):1858-1864. doi: 10.2967/jnumed.116.176206. Epub 2016 Aug 11.

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). 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 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.

Keywords: 89Zr- IAB2M; PSMA; dosimetry; minibody; prostate cancer imaging.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Antibodies, Monoclonal
  • Antigens, Surface / immunology*
  • Biological Transport
  • Carrier Proteins / immunology*
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacokinetics*
  • Glutamate Carboxypeptidase II / immunology*
  • Half-Life
  • Humans
  • Immunoglobulin Fragments / immunology*
  • Immunoglobulin Fragments / metabolism
  • Immunoglobulins / immunology*
  • Immunoglobulins / metabolism
  • Male
  • Neoplasm Metastasis
  • Positron Emission Tomography Computed Tomography / methods*
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Radiation Dosage
  • Radiometry
  • Tissue Distribution

Substances

  • Antibodies, Monoclonal
  • Antigens, Surface
  • Carrier Proteins
  • Immunoglobulin Fragments
  • Immunoglobulins
  • Minibody (WT)
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II