Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Institute for Frontier Science Initiative, Kanazawa University, Kanazawa 920-1192, Japan.
Nucl Med Biol. 2022 Nov-Dec;114-115:34-41. doi: 10.1016/j.nucmedbio.2022.08.004. Epub 2022 Aug 24.
Prostate cancer frequently metastasizes to the bone. Because patients with bone metastases suffer from skeletal-related events, the diagnosis and treatment of bone metastases in the early stage are important. In this study, to improve the sensitivity of detecting bone metastases in patients with prostate cancer, we designed, synthesized, and evaluated a multifunctional radiotracer, [Ga]Ga-D-PSMA-617 ([Ga]3), with an undeca-aspartic acid as a bone-seeking moiety between [Ga]Ga-DOTA and a prostate-specific membrane antigen (PSMA) ligand based on the lysine-urea-glutamate motif. [Ga]3 showed a high affinity for hydroxyapatite and high uptake in PSMA-positive LNCaP cells. Moreover, in biodistribution experiments using tumor-bearing mice, [Ga]3 exhibited high accumulation in the bone and PSMA-positive tumor although the accumulation of [Ga]3 in the PSMA-positive tumor was lower than that of [Ga]Ga-PSMA-617. This study provides valuable information for developing radiotheranostic probes combining multiple carriers with different mechanisms.
前列腺癌常转移至骨骼。由于骨转移患者会发生与骨骼相关的事件，因此早期诊断和治疗骨转移非常重要。在这项研究中，为了提高前列腺癌患者骨转移检测的灵敏度，我们设计、合成并评估了一种多功能放射性示踪剂[Ga]Ga-D-PSMA-617([Ga]3)，该示踪剂以天冬氨酸作为连接物，将[Ga]Ga-DOTA 和基于赖氨酸-脲-谷氨酸基序的前列腺特异性膜抗原（PSMA）配体连接起来。[Ga]3 对羟磷灰石具有高亲和力，并且在 PSMA 阳性的 LNCaP 细胞中有高摄取率。此外，在荷瘤小鼠的生物分布实验中，[Ga]3 在骨和 PSMA 阳性肿瘤中有高蓄积，尽管[Ga]3 在 PSMA 阳性肿瘤中的蓄积低于[Ga]Ga-PSMA-617。本研究为开发结合不同机制的多种载体的放射性治疗探针提供了有价值的信息。
