Background: The gastrin-releasing peptide receptor (GRPr) is highly overexpressed in several solid tumors, including treatment-naïve and recurrent prostate cancer. [68Ga]Ga-RM2 is a well-established radiotracer for PET imaging of GRPr, and [177Lu]Lu-RM2 has been proposed as a therapeutic alternative for patients with heterogeneous and/or low expression of PSMA. In this study, we aimed to evaluate the expression of GRPr and PSMA in a group of patients diagnosed with castration-resistant prostate cancer (mCRPC) by means of PET imaging. Methods: Seventeen mCRPC patients referred for radio-ligand therapy (RLT) were enrolled and underwent [68Ga]Ga-PSMA-11 and [68Ga]Ga-RM2 PET/CT imaging, 8.8 ± 8.6 days apart, to compare the biodistribution of each tracer. Uptake in healthy organs and tumor lesions was assessed by SUV values, and tumor-to-background ratios were analyzed. Results: [68Ga]Ga-PSMA-11 showed significantly higher uptake in tumor lesions in bone, lymph nodes, prostate, and soft tissues and detected 23% more lesions compared to [68Ga]Ga-RM2. In 4/17 patients (23.5%), the biodistribution of both tracers was comparable. Conclusions: Our results show that in our cohort of mCRPC patients, PSMA expression was higher compared to GRPr. Nevertheless, RLT with [177Lu]Lu-RM2 may be an alternative treatment option for selected patients or patients in earlier disease stages, such as biochemical recurrence.
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