Gallium-68 PSMA-617

We aimed to compare the diagnostic performance of 68Ga-P16-093 and 68Ga-PSMA-617 PET/CT in primary prostate cancer (PCa) patients.

Thirty untreated primary PCa patients were enrolled. Each patient underwent 68Ga-P16-093 and 68Ga-PSMA-617 PET/CT within a week. In addition to visual analysis, SUV was measured for semiquantitative comparison and correlation analysis.

68Ga-P16-093 PET/CT detected more positive tumors than 68Ga-PSMA-617 PET/CT (67 vs 56, P = 0.002), especially for intraprostatic lesions (29 vs 24, P = 0.025) and lymph node metastases (23 vs 17, P = 0.034). Further, 68Ga-P16-093 PET/CT exhibited significantly higher SUVmax of matched tumors (18.3 ± 14.4 vs 13.9 ± 11.8, P < 0.001). Besides, the SUVmax of high-risk patients (based on D’Amico classification) on 68Ga-P16-093 PET/CT was significantly higher than that of low- and intermediate-risk PCa patients (20.9 ± 9.9 vs 8.9 ± 9.1 vs 10.1 ± 5.2, P = 0.007). The SUVmax of tumor measured by 68Ga-P16-093 PET/CT had a moderate association with biopsy Gleason score (r = 0.462, P = 0.005) and prostate-specific antigen value (r = 0.491, P = 0.002), and significantly correlated with PSMA expression (r = 0.732, P < 0.001).

68Ga-P16-093 PET/CT exhibited higher tumor uptake and potentially better tumor detection capability than 68Ga-PSMA-617 PET/CT, which suggested that 68Ga-P16-093 may be more suitable in the diagnosis and staging of primary PCa patients.

Considering the wide range of therapeutic options for localized prostate cancer (e.g., active surveillance, radiation-beam therapy, focal therapy, and radical prostatectomy), accurate assessment of the aggressiveness and localization of primary prostate cancer lesions is essential for treatment decision making. National Comprehensive Cancer Network guidelines recognize prostate-specific membrane antigen (PSMA) PET/CT for use in initial staging of high-risk primary prostate cancer. The gastrin-releasing peptide receptor (GRP-R) is a neuropeptide receptor overexpressed by low-risk prostate cancer cells. We aimed to perform the first (to our knowledge) prospective head-to-head comparison of PSMA- and GRP-R-targeted imaging at initial staging to understand how PSMA PET and GRP-R PET can be used or combined in clinical practice. Methods: This was a prospective, single-center, diagnostic cross-sectional imaging study using anonymized, masked, and independent interpretations of paired PET/CT studies in 22 patients with ⁶⁸Ga-PSMA-617 (a radiolabeled PSMA inhibitor) and ⁶⁸Ga-RM2 (⁶⁸Ga-DOTA-4-amino-1-carboxymethylpiperidine-d-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2, a radiolabeled GRP-R antagonist). We enrolled patients with newly diagnosed, biopsy-proven prostate cancer. None had received neoadjuvant hormone therapy or chemotherapy, and all underwent extended pelvic lymph node dissection. Histologic findings served as a reference. Results: On a lesion-based analysis (including lesions < 0.1 cm³), ⁶⁸Ga-PSMA-617 PET/CT detected 74.3% (26/35) of all tumor lesions and ⁶⁸Ga-RM2 PET/CT detected 78.1% (25/32; 1 patient could not be offered ⁶⁸Ga-RM2 PET/CT). Paired examinations showed positive uptake of the 2 tracers in 21 of 32 lesions (65.6%), negative uptake in 5 of 32 lesions (15.6%), and discordant uptake in 6 of 32 lesions (18.8%). Uptake of ⁶⁸Ga-PSMA-617 was higher when the International Society of Urological Pathology (ISUP) score was at least 4 versus at least 1 (P < 0.0001) or 2 (P = 0.0002). There were no significant differences in uptake between ISUP scores for ⁶⁸Ga-RM2. Median ⁶⁸Ga-RM2 SUV_max was significantly higher than median ⁶⁸Ga-PSMA-617 SUV_max in the ISUP-2 subgroup (P = 0.01). Conclusion: ⁶⁸Ga-PSMA-617 PET/CT is useful to depict higher, more clinically significant ISUP score lesions, and ⁶⁸Ga-RM2 PET/CT has a higher detection rate for low-ISUP tumors. Combining PSMA PET and GRP-R PET allows for better classification of intraprostatic lesions.