Cao Jianpeng, Sun Zhanliang, Zhou Zhijun, Huang Yilin, Peng Dengsai, Jiang Xue, Chen Yue
Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, China.
Sci Rep. 2025 Jun 6;15(1):20000. doi: 10.1038/s41598-025-05344-y.
Small-molecule inhibitors targeting prostate-specific membrane antigen (PSMA) have demonstrated promising results in the theranostics of prostate cancer (PCa). We designed and synthesized a novel small-molecule PSMA inhibitor, SC691. This study aimed to conduct a preliminary clinical prospective investigation of Ga-SC691. Following predefined inclusion/exclusion criteria, this study enrolled 7 healthy volunteers and 12 patients with PCa. Patients underwent Ga-SC691 and Ga-PSMA-11 PET/CT imaging within one week. PET/CT data were analyzed using a uWS-MI workstation.Ga-SC691 demonstrated favorable safety profiles in all participants. Ga-SC691 was primarily excreted via the urinary system, exhibiting a biodistribution similar to that of Ga-PSMA-11. Compared to Ga-PSMA-11, Ga-SC691 showed lower non-specific organs uptake, particularly in the liver: 2.5 ± 0.7 vs. 4.1 ± 1.6 (P = 0.002). Furthermore, Ga-SC691 and Ga-PSMA-11 detected the same number and location of PSMA-positive lesions in PCa primary tumors, bone metastases, and lymph nodes metastases. Notably, Ga-SC691 demonstrated higher tumor-to-non-tumor ratios (T/NT) (P < 0.05). In conclusions, as a novel small-molecule PSMA inhibitor, SC691 exhibits a favorable safety profile, biodistribution, and diagnostic performance, suggesting its potential as a valuable agent for PCa imaging and therapy. The lower non-specific organ uptake further supports its promise for theranostic applications.
靶向前列腺特异性膜抗原（PSMA）的小分子抑制剂在前列腺癌（PCa）的诊疗中已显示出有前景的结果。我们设计并合成了一种新型小分子PSMA抑制剂SC691。本研究旨在对Ga-SC691进行初步的临床前瞻性研究。按照预先定义的纳入/排除标准，本研究招募了7名健康志愿者和12名PCa患者。患者在一周内接受了Ga-SC691和Ga-PSMA-11 PET/CT成像检查。使用uWS-MI工作站对PET/CT数据进行分析。Ga-SC691在所有参与者中显示出良好的安全性。Ga-SC691主要通过泌尿系统排泄，其生物分布与Ga-PSMA-11相似。与Ga-PSMA-11相比，Ga-SC691显示出较低的非特异性器官摄取，尤其是在肝脏：2.5±0.7 vs. 4.1±1.6（P = 0.002）。此外，Ga-SC691和Ga-PSMA-11在PCa原发肿瘤、骨转移和淋巴结转移中检测到相同数量和位置的PSMA阳性病变。值得注意的是，Ga-SC691显示出更高的肿瘤与非肿瘤比值（T/NT）（P < 0.05）。总之，作为一种新型小分子PSMA抑制剂，SC691具有良好的安全性、生物分布和诊断性能，表明其作为PCa成像和治疗的有价值药物的潜力。较低的非特异性器官摄取进一步支持了其在诊疗应用中的前景。
