The first-in-human preclinical evaluation of the new probe [123I]I-PSMA-7 for real-time intraoperative targeted biopsy and SPECT/CT imaging in prostate cancer.

Purpose: PSMA/PET has been increasingly used to detect PCa, and PSMA/PET-guided biopsy has shown promising results. However, it cannot be confirmed immediately whether the tissues are the targeted area. In this study, we aimed to develop a novel probe, [I]I-PSMA-7. First, we hope that [I]I-PSMA-7 can provide instant confirmation for prostate biopsy. Second, we hope it will help detect PCa.

Methods: We synthesized a high-affinity probe, [I]I-PSMA-7, and evaluated its properties. We included ten patients with suspected PCa and divided them into two groups. The injection and biopsy were approximately 24 h apart. The activity in biopsy lesions was measured as the cpm by a γ-counter. Moreover, we enrolled 3 patients to evaluate the potential of [I]I-PSMA-7 for detecting PCa.

Results: Animal experiments verified the safety, targeting and effectiveness of [I]I-PSMA-7, and the tumor-to-muscle ratio was greatest at 24 h, which confirmed the results of this study in humans. After injection of 185MBq [I]I-PSMA-7, 18/55 cores were positive, and the cpm was significantly greater (4345 ± 3547 vs. 714 ± 547, P < 0.001), with an AUC of 0.97 and a cutoff of 1312 (sens/spec of 94.40%/91.90%). At a lower dose, 10/55 biopsy cores were cancerous, and the cpm was 2446 ± 1622 vs. 153 ± 112 (P < 0.001). The AUC was 1, with a cutoff value of 490 (sens/spec of 100%). When the radiopharmaceuticals were added to 370 MBq, we achieved better SPECT/CT imaging.

Conclusion: With the aid of [I]I-PSMA-7 and via cpm-based biopsy, we can reduce the number of biopsies to a minimum operation. [I]I-PSMA-7 PSMA SPECT/CT can also provide good imaging results.

Trial Registration: Chinese Clinical trial registry ChiCTR2300069745, Registered 24 March 2023.