<p>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 (<i>P</i> = 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) (<i>P</i> &lt; 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.</p>