Department of Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China.
Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
Bioorg Med Chem Lett. 2023 Jul 15;91:129382. doi: 10.1016/j.bmcl.2023.129382. Epub 2023 Jun 20.
Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synthesized seven ODAP-Urea-Lys derivatives characterized with p-bromobenzyl group conjugated to lysine. The ligands showed medium-to-high potency, with K values ranging from 27.9 nM to 0.94 nM. The ligands could be efficiently radiolabeled with Ga, in high purity. Radioligands were stable and showed PSMA specific cellular uptake, in PSMA LNCaP cells and PSMA 22Rv1 cells over PSMA PC3 cells. MicroPET imaging was performed in 22Rv1 tumor-bearing mice and Ga-ligand-1 showed the best characteristics among the seven ligands, with the highest tumor uptake (SUVmax: 0.56 ± 0.07). A biodistribution study was also performed. ODAP-Urea-Lys-p-bromobenzyl could be used to image prostate cancer in vivo, and the ligands could have high binding potency. The future investigation is still necessary to improve the tumor-specific uptake of this class of ligands and reducing the non-specific uptake in normal organs.
前列腺特异性膜抗原（PSMA）已被证明是诊断和治疗前列腺癌（PCa）的特异性靶点。最近，草酰二氨基丙酸（ODAP）-尿素基配体显示出作为开发用于成像 PCa 的放射性示踪剂的新型支架的潜力。在这项研究中，我们合成了七种具有与赖氨酸共轭的对溴苄基的 ODAP-Urea-Lys 衍生物。这些配体表现出中等至高的效力，K 值范围为 27.9 nM 至 0.94 nM。配体可以用 Ga 高效标记，纯度高。放射性配体稳定，在 PSMA LNCaP 细胞和 PSMA 22Rv1 细胞中表现出 PSMA 特异性细胞摄取，而在 PSMA PC3 细胞中则没有。在 22Rv1 荷瘤小鼠中进行了 microPET 成像，在这七种配体中，Ga-配体-1 表现出最佳特性，肿瘤摄取最高（SUVmax：0.56±0.07）。还进行了生物分布研究。ODAP-Urea-Lys-p-溴苄基可用于体内成像前列腺癌，并且配体可以具有高结合效力。未来仍有必要研究提高此类配体的肿瘤特异性摄取并减少正常器官的非特异性摄取。
