68Ga-PSMA and 68Ga-DOTA-RM2 PET/MRI in Recurrent Prostate Cancer: Diagnostic Performance and Association with Clinical and Histopathological Data

Simple Summary Prostate cancer (PCa) relapse occurs in up to 50% of patients after radical treatment. Once PCa recurrence is detected, a precise identification of the number and sites of recurrence is necessary to tailor the treatment on the patient's needs. Positron emission tomography (PET) plays a pivotal role in this clinical setting and new radiotracers have been developed to improve its performance. While Ga-68-PSMA is a well-established radiotracer for PCa recurrence detection, Ga-68-DOTA-RM2 is a recently proposed tracer that targets the gastrin-releasing peptide receptors that are overexpressed in prostate cancer. In this work, the performance of Ga-68-PSMA and Ga-68-DOTA-RM2 PET/MRI in identifying recurrent disease were compared on the same cohort, using the same study protocol, as this is the only way to assess whether one outperforms the other and therefore should be preferred in clinical practice. Furthermore, the association between PET findings and clinical and histopathological characteristics was investigated to find potential biomarkers. The aim of the present study is to investigate and compare the performances of Ga-68-PSMA and Ga-68-DOTA-RM2 PET/MRI in identifying recurrent prostate cancer (PCa) after primary treatment and to explore the association of dual-tracer PET findings with clinical and histopathological characteristics. Thirty-five patients with biochemical relapse (BCR) of PCa underwent Ga-68 PSMA PET/MRI for restaging purpose, with 31/35 also undergoing Ga-68-DOTA-RM2 PET/MRI scan within 16 days (mean: 3 days, range: 2-16 days). Qualitative and quantitative image analysis has been performed by comparing Ga-68-PSMA and Ga-68-DOTA-RM2 PET/MRI findings both on a patient and lesion basis. Clinical and instrumental follow-up was used to validate PET findings. Fisher's exact test and Mann-Whitney U test were used to investigate the association between dual-tracer PET findings, clinical and histopathological data. p-value significance was defined below the 0.05 level. Patients' mean age was 70 years (range: 49-84) and mean PSA at time of PET/MR scans was 1.88 ng/mL (range: 0.21-14.4). A higher detection rate was observed for Ga-68-PSMA PET/MRI, with more lesions being detected compared to Ga-68-DOTA-RM2 PET/MRI (26/35 patients, 95 lesions vs. 15/31 patients, 41 lesions; p = 0.016 and 0.002). Ga-68-PSMA and Ga-68-DOTA-RM2 PET/MRI findings were discordant in 11/31 patients; among these, 10 were Ga-68-PSMA positive (9/10 confirmed as true positive and 1/10 as false positive by follow-up examination). Patients with higher levels of PSA and shorter PSA doubling time (DT) presented more lesions on Ga-68-PSMA PET/MRI (p = 0.006 and 0.044), while no association was found between PET findings and Gleason score. Ga-68-PSMA has a higher detection rate than Ga-68-DOTA-RM2 in detecting PCa recurrence. The number of Ga-68-PSMA PET positive lesions is associated with higher levels of PSA and shorter PSA DT, thus representing potential prognostic factors.