We assessed the value of fusion 18F-fluoromethylcholine (18F-choline) PET/MRI for image-guided (targeted) prostate biopsies to detect significant prostate cancer (Gleason ≥ 3 + 4) compared with standard (systematic 12-core) biopsies. Methods: Within an ongoing prospective clinical trial, hybrid 18F-choline PET/CT and multiparametric 3T MRI (mpMRI) of the pelvis were performed in 36 subjects with a rising prostate-specific antigen for known (n = 15) or suspected (n = 21) prostate cancer before a prostate biopsy procedure. PET and T2-weighted MR volumes of the prostate were spatially registered using commercially available software. Biopsy targets were selected on the basis of visual appearance on MRI and graded as low, intermediate, or high risk for significant disease. Volumes of interest were defined for MR-identified lesions. 18F-choline uptake measures were obtained from the MR target and a mirrored background volume of interest. The biopsy procedure was performed after registration of real-time transrectal ultrasound with T2-weighted MR and included image-guided cores plus standard cores. Histologic results were determined from standard and targeted biopsy cores as well as prostatectomy specimens (n = 10). Read more.