Abstract Background Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). In a prospective study, the feasibility of ¹⁸F-MK-9470 positron emission tomography (PET) imaging in patients with primary and metastatic PCa was evaluated. Methods Eight patients were included and underwent ¹⁸F-MK-9470 PET/CT imaging. For five patients with primary PCa, dynamic PET/CT imaging was performed over three acquisition intervals (0 to 30, 60 to 90 and 120 to 150 min post-injection). In malignant and benign prostate tissue regions, time activity curves of the mean standardized uptake value (SUV_mean) were determined as well as the corresponding area under the curve to compare ¹⁸F-MK-9470 uptake over time. Muscle uptake of ¹⁸F-MK-9470 was used as reference for non-specific binding. Magnetic resonance imaging (MRI) was used as anatomical reference and for delineating intraprostatic tumours. Histological and immunohistochemical (IHC) examination was performed on the whole-mount histopathology sections of four patients who underwent radical prostatectomy to assess the MRI-based tumour versus benign tissue classification. For three patients with proven advanced metastatic disease, two static PET/CTs were performed 1 and 3 h post-injection. ¹⁸F-MK-9470 uptake was evaluated in bone lesions of metastatic PCa by comparing SUV_mean values of metastases with these of the contralateral bone tissue. Results ¹⁸F-MK-9470 uptake was significantly higher in benign and malignant prostate tissue compared to muscle, but it did not differ between both prostate tissue compartments. IHC findings of corresponding prostatic histopathological sections indicated weak CB1R expression in locally confined PCa, which was not visualized with ¹⁸F-MK-9470 PET. Metastases in the axial skeleton could not be detected while some metastases in the appendicular skeleton showed higher ¹⁸F-MK-9470 uptake as compared to the uptake in contralateral normal bone. Conclusions ¹⁸F-MK-9470 PET could not detect local PCa or bone metastases in the axial skeleton but was able to visualize metastases in the appendicular skeleton. Based on these pilot observations, it seems unlikely that CB1R PET will play a significant role in the evaluation of PCa.