Joraku Akira, Hatano Kentaro, Kawai Koji, Kandori Shuya, Kojima Takahiro, Fukumitsu Nobuyoshi, Isobe Tomonori, Mori Yutaro, Sakata Muneyuki, Hara Tadashi, Nasu Katsuhiro, Minami Manabu, Iizumi Yuichi, Nishiyama Hiroyuki
Department of Urology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Department of Applied Molecular Imaging, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan.
Ann Nucl Med. 2019 Feb;33(2):119-127. doi: 10.1007/s12149-018-1312-6. Epub 2018 Nov 7.
We conducted the present phase I/IIa positron emission tomography (PET) imaging study with Zr conjugated with desferroxamine-IAB2M (Zr-Df-IAB2M), an anti-prostate-specific membrane-antigen minibody, to assess its safety and feasibility in patients with urological cancer.
Zr-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 Zr-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 Zr-immuno-PET imaging for 13 patients with prostate cancer and 4 patients with other urological cancer.
The administration of Zr-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 Zr-Df-IAB2M by 24 or 48 h imaging.
Administration of Zr-Df-IAB2M was well-tolerated and safe in terms of adverse events and radiation exposure and protection. Zr-Df-IAB2M is feasible for usage by long-distance transportation. Further studies are warranted for analysis of its use for tumor lesion detection (UMIN000015356).
我们开展了本项I/IIa期正电子发射断层扫描（PET）成像研究，使用与去铁胺 - IAB2M（Zr - Df - IAB2M，一种抗前列腺特异性膜抗原微型抗体）共轭的锆，以评估其在泌尿系统癌症患者中的安全性和可行性。
Zr - Df - IAB2M由IBA Molecular公司（美国新泽西州萨默塞特）合成，并空运至筑波分子影像中心（日本茨城县筑波）。17例患者接受了总质量剂量为10 mg的74 MBq（2 mCi）Zr - Df - IAB2M。估计了全身和血浆清除率、正常器官和病变摄取以及辐射吸收剂量。我们还对13例前列腺癌患者和4例其他泌尿系统癌症患者初步测试了Zr免疫PET成像的性能。
Zr - Df - IAB2M的给药耐受性良好，所有患者均未观察到与输注相关的反应。实验室参数、生命体征或其他参数均未发现不良事件。血浆清除呈双相性，初始为快速相（t1/2快速：10.1±3.4小时），随后为缓慢相（t1/2缓慢：49.0±22.7小时）。全身放射性半衰期（WB t1/2）为237±9小时。在肝脏和肾脏中观察到最高吸收辐射剂量为1.67 mGy/MBq。有效剂量为0.68±0.08 mSv/MBq。在注射后第1天，距离患者0.5 m处的辐射剂量率为8.67 µSv/h，在注射后5天降至2.26 µSv/h。通过24或48小时成像，Zr - Df - IAB2M检测到了骨转移和淋巴结转移。
就不良事件以及辐射暴露和防护而言，Zr - Df - IAB2M的给药耐受性良好且安全。Zr - Df - IAB2M通过长途运输使用是可行的。有必要进一步研究分析其用于肿瘤病变检测的情况（UMIN000015356）。
