Abstract
BackgroundPreclinical 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.MethodsEight 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 (SUVmean) 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 SUVmean values of metastases with these of the contralateral bone tissue.Results18F-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.Conclusions18F-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.
Highlights
Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa)
An elevated expression of both cannabinoid receptors has been demonstrated in vitro in PCa cell lines compared to the expression levels in normal prostatic cells [3], most research efforts to date have concentrated on the clinical potential of CB1R in PCa
The present study aimed to evaluate the utility of 18F-MK-9470 positron emission tomography (PET)/CT to detect CB1R expression in both primary and metastatic PCa
Summary
Preclinical and histological data show overexpression of the type 1 cannabinoid receptor (CB1R) in prostate carcinoma (PCa). Treatments including radical prostatectomy (RP) and radiotherapy (RT) intend to cure localized PCa; within 2 to 4 years recurrent, mostly incurable disease occurs in 30% to 50% of all patients. An elevated expression of both cannabinoid receptors has been demonstrated in vitro in PCa cell lines compared to the expression levels in normal prostatic cells [3], most research efforts to date have concentrated on the clinical potential of CB1R in PCa. CB1R expression does not correlate with increasing tumour grade [9]. Increased CB1R density was further related to increased levels of fatty acid amide hydrolase and phosphorylated epidermal growth factor receptor (pEGFR) expression in PCa specimens. The potential of CB1R-based therapeutics reducing cannabinoid metabolism and tumour proliferation was discussed [11,12]
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