2. Academic Validation
  3. Preliminary clinical study of p-iodo benzoyl moiety-modified PSMA inhibitors and prospective comparison with 68Ga-PSMA-11

Preliminary clinical study of p-iodo benzoyl moiety-modified PSMA inhibitors and prospective comparison with 68Ga-PSMA-11

  • Sci Rep. 2025 Jun 6;15(1):20000. doi: 10.1038/s41598-025-05344-y.
Jianpeng Cao # 1 2 3,  Zhanliang Sun # 1 2 3,  Zhijun Zhou # 1 2 3,  Yilin Huang 4,  Dengsai Peng 1 2 3,  Xue Jiang 5,  Yue Chen 6 7 8
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China.
  • 2 Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, China.
  • 3 PR China. Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China.
  • 4 Department of Nuclear Medicine, Chongqing University Cancer Hospital, Chongqing, China.
  • 5 Department of Nuclear Medicine, Second Affiliated Hospital of Chengdu Medical College (China National Nuclear Corporation 416 Hospital), Chengdu, 610000, People's Republic of China.
  • 6 Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People's Republic of China. chenyue5523@126.com.
  • 7 Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan, China. chenyue5523@126.com.
  • 8 PR China. Academician (Expert) Workstation of Sichuan Province, Luzhou, Sichuan, People's Republic of China. chenyue5523@126.com.
  • # Contributed equally.
PMID: 40481129 DOI: 10.1038/s41598-025-05344-y
Abstract

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 68Ga-SC691. Following predefined inclusion/exclusion criteria, this study enrolled 7 healthy volunteers and 12 patients with PCa. Patients underwent 68Ga-SC691 and 68Ga-PSMA-11 PET/CT imaging within one week. PET/CT data were analyzed using a uWS-MI workstation.68Ga-SC691 demonstrated favorable safety profiles in all participants. 68Ga-SC691 was primarily excreted via the urinary system, exhibiting a biodistribution similar to that of 68Ga-PSMA-11. Compared to 68Ga-PSMA-11, 68Ga-SC691 showed lower non-specific organs uptake, particularly in the liver: 2.5 ± 0.7 vs. 4.1 ± 1.6 (P = 0.002). Furthermore, 68Ga-SC691 and 68Ga-PSMA-11 detected the same number and location of PSMA-positive lesions in PCa primary tumors, bone metastases, and lymph nodes metastases. Notably, 68Ga-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.

Keywords

68Ga-PSMA-11; 68Ga-SC691; PET/CT; Prostate Cancer; Prostate-Specific membrane antigen (PSMA).

Figures
Products