A prospective comparative study of [ 68 Ga]Ga-RM26 and [ 68 Ga]Ga-PSMA-617 PET/CT imaging in suspicious prostate cancer

Purpose Prostate-specific membrane antigen (PSMA)–based PET/CT imaging has limitations in the diagnosis of prostate cancer (PCa). We recruited 207 participants with suspicious PCa to perform PET/CT imaging with radiolabeled gastrin-releasing peptide receptor (GRPR) antagonist, [ 68 Ga]Ga-RM26, and compare with [ 68 Ga]Ga-PSMA-617 and histopathology. Methods Every participant with suspicious PCa was scanned with both [ 68 Ga]Ga-RM26 and [ 68 Ga]Ga-PSMA-617 PET/CT. PET/CT imaging was compared using pathologic specimens as a reference standard. Results Of the 207 participants analyzed, 125 had cancer, and 82 were diagnosed with benign prostatic hyperplasia (BPH). The sensitivity and specificity of [ 68 Ga]Ga-RM26 and [ 68 Ga]Ga-PSMA-617 PET/CT imaging differed significantly for detecting clinically significant PCa. The area under the ROC curve (AUC) was 0.54 for [ 68 Ga]Ga-RM26 PET/CT and 0.91 for [ 68 Ga]Ga-PSMA-617 PET/CT in detecting PCa. For clinically significant PCa imaging, the AUCs were 0.51 vs. 0.93, respectively. [ 68 Ga]Ga-RM26 PET/CT imaging had higher sensitivity for PCa with Gleason score (GS) = 6 ( p = 0.03) than [ 68 Ga]Ga-PSMA-617 PET/CT but poor specificity (20.73%). In the group with PSA < 10 ng/mL, the sensitivity, specificity, and AUC of [ 68 Ga]Ga-RM26 PET/CT were lower than [ 68 Ga]Ga-PSMA-617 PET/CT (60.00% vs. 80.30%, p = 0.12, 23.26% vs. 88.37%, p = 0.000, and 0.524 vs. 0.822, p = 0.000, respectively). [ 68 Ga]Ga-RM26 PET/CT exhibited significantly higher SUVmax in specimens with GS = 6 ( p = 0.04) and in the low-risk group ( p = 0.01), and its uptake did not increase with PSA level, GS, or clinical stage. Conclusion This prospective study provided evidence for the superior accuracy of [ 68 Ga]Ga-PSMA-617 PET/CT over [ 68 Ga]Ga-RM26 PET/CT in detecting more clinically significant PCa. [ 68 Ga]Ga-RM26 PET/CT showed an advantage for imaging low-risk PCa.