Phase I/IIa PET imaging study with 89zirconium labeled anti-PSMA minibody for urological malignancies

Ann Nucl Med. 2019 Feb;33(2):119-127. doi: 10.1007/s12149-018-1312-6. Epub 2018 Nov 7.

Abstract

Objective: We conducted the present phase I/IIa positron emission tomography (PET) imaging study with 89Zr conjugated with desferroxamine-IAB2M (89Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer.

Methods: 89Zr-Df-IAB2M was synthetized by IBA Molecular (Somerset, NJ, USA) and transported by air to Tsukuba Molecular Imaging Center (Tsukuba, Ibaraki, Japan).17 patients received 74 MBq (2 mCi) of 89Zr-Df-IAB2M at total mass doses of 10 mg. Whole-body and plasma clearance, normal-organ and lesion uptake, and radiation absorbed dose were estimated. We also preliminarily tested the performance of 89Zr-immuno-PET imaging for 13 patients with prostate cancer and 4 patients with other urological cancer.

Results: The administration of 89Zr-Df-IAB2M was well-tolerated, and no infusion-related reactions were observed in any patient. No adverse events were noted in the laboratory parameters, vital signs, or other parameters. The plasma clearance was biphasic, with an initial rapid phase (t 1/2 fast: 10.1 ± 3.4 h) followed by a slow phase (t 1/2 slow: 49.0 ± 22.7 h). The half-life of radioactivity in the whole body (WB t1/2) was 237 ± 9 h. The highest absorbed radiation dose was 1.67 mGy/MBq, observed in the liver and kidney. The effective dose was 0.68 ± 0.08 mSv/MBq. The radiation dose rate at 0.5 m distance from the patient was 8.67 µSv/h on day 1, and decreased to 2.26 µSv/h at 5 days after injection. Both bone and lymph node metastases were detected with 89Zr-Df-IAB2M by 24 or 48 h imaging.

Conclusions: Administration of 89Zr-Df-IAB2M was well-tolerated and safe in terms of adverse events and radiation exposure and protection. 89Zr-Df-IAB2M is feasible for usage by long-distance transportation. Further studies are warranted for analysis of its use for tumor lesion detection (UMIN000015356).

Keywords: 89Zirconium-labeled tracer; Clinical trial; Minibody; PET; Prostate-specific membrane antigen; Urological cancer.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Deferoxamine* / adverse effects
  • Feasibility Studies
  • Female
  • Humans
  • Isotope Labeling
  • Male
  • Middle Aged
  • Positron-Emission Tomography*
  • Radioisotopes*
  • Safety
  • Urologic Neoplasms / diagnostic imaging*
  • Zirconium*

Substances

  • Radioisotopes
  • Zirconium
  • Deferoxamine
  • Zirconium-89