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?

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.