Prospective Comparison of68Ga-NeoB and68Ga-PSMA-R2 PET/MRI in Patients with Biochemically Recurrent Prostate Cancer

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptors are both overexpressed in prostate cancer (PC) but may provide complementary information.⁶⁸Ga-PSMA-R2 and ⁶⁸Ga-NeoB (DOTA-p-aminomethylaniline-diglycolic acid-DPhe-Gln-Trp-Ala-Val-Gly-His-NH-CH[CH₂-CH(CH₃)₂]₂) are novel PET radiopharmaceuticals that were developed for theranostic use. In this phase II imaging study, we assessed the feasibility, safety, and diagnostic performance of ⁶⁸Ga-NeoB and ⁶⁸Ga-PSMA-R2 PET/MRI for detection of biochemically recurrent PC. Methods: We prospectively enrolled 27 men with suspected biochemically recurrent PC after initial treatment but noncontributory conventional imaging results (negative or equivocal findings on MRI, CT, and/or bone scan). Participants underwent ⁶⁸Ga-NeoB and ⁶⁸Ga-PSMA-R2 PET/MRI within 2 wk in noncontrolled order. The SUV_max of putative PC lesions was measured and compared with a composite reference standard (histopathology, follow-up imaging, prostate-specific antigen change). The SUV_max and SUV_mean of background organs were measured. Vital signs were recorded before injection of the radiopharmaceuticals and after the scans. Adverse events were recorded up to 72 h after each scan. Results: The prostate-specific antigen level at enrollment was 3.5 ± 3.9 ng/mL (range, 0.3-13.5 ng/mL). ⁶⁸Ga-NeoB PET/MRI detected 31 lesions in 18 patients (66.7%), whereas ⁶⁸Ga-PSMA-R2 identified 20 lesions in 15 participants (55.6%). ⁶⁸Ga-NeoB PET/MRI showed higher sensitivity (85.7% vs. 71.4%), accuracy (88.9% vs. 77.8%), and negative predictive value (66.7% vs. 50.0%) than ⁶⁸Ga-PSMA-R2, whereas specificity and positive predictive value were equally high (100.0% for both). In 6 patients, ⁶⁸Ga-NeoB PET/MRI identified 14 lesions that were false-negative on ⁶⁸Ga-PSMA-R2 PET/MRI. The mean lesion SUV_max was 6.6 ± 3.2 (range, 2.9-13.2) for ⁶⁸Ga-NeoB and 4.4 ± 1.5 (range, 2.6-8.8) for ⁶⁸Ga-PSMA-R2 (P = 0.019). Overall lower uptake was noted in tumors and background organs for ⁶⁸Ga-PSMA-R2. There were no significant changes in vital signs before and after the scans. No adverse events were reported in the 72-h period after scans. Conclusion: ⁶⁸Ga-NeoB and ⁶⁸Ga-PSMA-R2 are safe for diagnostic imaging. ⁶⁸Ga-NeoB PET/MRI showed better diagnostic performance than ⁶⁸Ga-PSMA-R2. ⁶⁸Ga-PSMA-R2 showed overall lower uptake, equally in background organs and tumors, and might therefore not be an ideal theranostic compound. Further evaluation in larger cohorts is needed to confirm our preliminary data.