Df-IA2BM-Zr-89

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.

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.

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.

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).

Tumor angiogenesis has attracted increasing attention because of its potential as a valuable marker in the differential diagnosis of brain tumors as well as a novel therapeutic target. Prostate-specific membrane antigen (PSMA) is expressed by the neovasculature endothelium of some tumors, with little to no expression by the tumor cells or normal vasculature endothelium. The aim of this study was to investigate the potential of PSMA for the evaluation of the tumor neovasculature of various brain tumors and the possibility of detecting PSMA expression in brain tumors using PET imaging with ⁸⁹Zr-Df-IAB2M (anti-PSMA minibody). Eighty-three tissue specimens including gliomas, metastatic brain tumors, primary central nervous system lymphomas (PCNSL), or radiation necroses were analyzed by immunohistochemical staining with PSMA antibody. ⁸⁹Zr-Df-IAB2M PET scans were performed in three patients with recurrent high-grade gliomas or metastatic brain tumor. PSMA was highly expressed in the vascular endothelium of high-grade glioma and metastatic brain tumor, whereas PSMA was poorly expressed in the vascular endothelium of PCNSL and radiation necrosis. PSMA expression in high-grade gliomas and a metastatic brain tumor was clearly visualized by PET imaging with ⁸⁹Zr-Df-IAB2M. Furthermore, a trend toward a positive correlation between the degree of ⁸⁹Zr-Df-IAB2M uptake and PSMA expression levels in tumor specimens was observed. PET imaging of PSMA using ⁸⁹Zr-Df-IAB2M may have potential value in the differential diagnosis of high-grade glioma from PCNSL or radiation necrosis as well as in the prediction of treatment efficacy and assessment of treatment response to bevacizumab therapy for high-grade glioma.