Awareness of the high rate of false positive [ 68 Ga]Ga-prostate specific membrane antigen-11 uptake in the prostate gland: can PET/MRI solve this problem?

Abstract

Objective: To assess the false positive gallium-68-labeled urea-based prostate-specific membrane antigen ( 68 Ga-PSMA) uptake rate in the prostate gland in patients with primary prostate cancer (PCa), and determine whether multiparametric prostate MRI (mpMRI) within hybrid PET/MRI can reduce false positives.

Methods: Fifty-one treatment-naive patients with PCa undergoing radical prostatectomy were prospectively recruited. All underwent 68 Ga-PSMA-11 PET/MRI with mpMRI. Images were assessed independently by the nuclear medicine physicians and radiologist using PRIMARY score and PIRADS v2.1, then jointly as fused PET/MRI. Radical prostatectomy followed imaging after a mean interval of 46 ± 32 days. Imaging findings were compared with postoperative histological mapping. Prostate was divided into sextants for lesion localization, and false positive uptake was recorded. Diagnostic performance metrics were calculated.

Results: Seven of 51 patients (13.7%) exhibited false positive PSMA uptake because of benign findings - asymmetrical central zone thickening, benign prostatic hyperplasia, or prostatitis. mpMRI was true negative in all. PET/MRI showed higher sensitivity and accuracy (74.9 and 83.0%) than PET (65.0 and 74.5%) and mpMRI (66.5 and 77.5%). For index lesion detection, PET/MRI had 92.2% sensitivity, outperforming PET (80.4%) and mpMRI (86.3%). PET/MRI was significantly more accurate than mpMRI ( P < 0.001) and PET ( P = 0.014), while PET and mpMRI were similar ( P = 0.770).

Conclusion: False positive 68 Ga-PSMA uptake is common and can affect clinical decisions, including focal therapy or recurrence assessment after radiotherapy. mpMRI helps clarify benign mimics, improving diagnostic accuracy. PET/MRI may offer more reliable assessment of PCa, potentially aiding focal therapy planning and posttreatment evaluation.

Keywords: PET; PET/MRI; PIRADS; PRIMARY score; false positive PSMA uptake; multiparametric prostate imaging; prostate cancer; prostate-specific membrane antigen.