Department of Nuclear Medicine, Korea Cancer Centre Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Division of Applied RI, Research Institute of Radiological & Medical Sciences, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Cancer Biother Radiopharm. 2022 Aug;37(6):417-423. doi: 10.1089/cbr.2020.4189. Epub 2021 Jan 12.
The goal of this research was to investigate the feasibility of Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (PET) imaging and biodistribution evaluation. PSMA I&T was labeled with Cu, and stability in human and mouse sera was evaluated. Prostate cancer cell lines were used for specific uptake assays (22RV1 for PSMA-positive, PC-3 for -negative). Both PC-3 and 22RV1 cells were transplanted into the left and right thighs in a mouse for PET/computed tomography (CT) imaging. Biodistribution was performed using 22RV1 tumor models. Labeling yield (decay corrected) of Cu-PSMA I&T was more than 95% compared to the free Cu peak. The serum stability of Cu-PSMA I&T was maintained at more than 90% until 60 h. Regarding the specific binding of Cu-PSMA I&T was 7.5-fold higher to 22RV1 cells than PC-3 cells ( < 0.001). On PET/CT imaging, more specific Cu-PSMA I&T uptake was observed to 22RV1 tumors than to PC-3 tumors. In the PSMA blocking study using 2-phosphonomethoxypropyl adenine (2-PMPA), the Cu-PSMA I&T signal significantly decreased in the 22RV1 tumor region. In the biodistribution study, the kidney uptake was the highest among all organs at 2 h (52.6 ± 20.8%ID/g) but sharply decreased at 24 and 48 h. Also, the liver showed similar uptake over time (range, 10-12%ID/g). On the contrary, Cu-PSMA I&T uptake of the tumors increased with time and peaked at 48 h (5.6 ± 0.1%ID/g). PSMA I&T labeled with Cu showed the feasibility of the PSMA specific PET imaging through and studies. Furthermore, Cu-PSMA I&T might be considered as the candidate of future clinical trial.
这项研究的目的是探讨在前列腺特异性膜抗原成像和治疗（PSMA I&T）中使用铜标记进行 PSMA 正电子发射断层扫描（PET）成像和生物分布评估的可行性。PSMA I&T 用 Cu 标记，并评估其在人血清和鼠血清中的稳定性。使用前列腺癌细胞系进行特异性摄取测定（22RV1 为 PSMA 阳性，PC-3 为阴性）。将 PC-3 和 22RV1 细胞分别移植到小鼠的左右大腿中进行 PET/计算机断层扫描（CT）成像。使用 22RV1 肿瘤模型进行生物分布研究。与游离 Cu 峰相比，Cu-PSMA I&T 的标记产率（衰减校正后）超过 95%。Cu-PSMA I&T 的血清稳定性在 60 小时内保持在 90%以上。关于 Cu-PSMA I&T 的特异性结合，22RV1 细胞的结合是 PC-3 细胞的 7.5 倍（ < 0.001）。在 PET/CT 成像中，与 PC-3 肿瘤相比，22RV1 肿瘤中观察到更多的特异性 Cu-PSMA I&T 摄取。在使用 2-磷甲氧基丙氨酸（2-PMPA）的 PSMA 阻断研究中，22RV1 肿瘤区域的 Cu-PSMA I&T 信号显著降低。在生物分布研究中，2 小时时肾脏摄取最高（52.6 ± 20.8%ID/g），但在 24 小时和 48 小时时急剧下降。同样，肝脏在整个时间内的摄取相似（范围为 10-12%ID/g）。相反，肿瘤中 Cu-PSMA I&T 的摄取随时间增加，并在 48 小时时达到峰值（5.6 ± 0.1%ID/g）。用 Cu 标记的 PSMA I&T 通过体内和体外研究显示了 PSMA 特异性 PET 成像的可行性。此外，Cu-PSMA I&T 可能被视为未来临床试验的候选药物。
