The relationship between tumor aggressiveness and cholinergic PET imaging in prostate cancer tissue. A proof-of-concept study.

It was recently shown that high-risk prostate carcinoma (PCa) exhibited parasympathetic neurogenesis. The PET tracer C-donepezil is a marker of parasympathetic innervation. Therefore, we studied if parasympathetic nerve density in PCa measured with C-donepezil PET correlated with PCa aggressiveness and if metastases could be visualized. Twenty-six patients were included into three groups with varying tumor aggressiveness. Dynamic and static PET scans were performed. Maximal standardized uptake values (SUV) were determined in lesions within the prostate, lymph nodes, and bones. SUV in primary PCa were compared between groups, and comparisons between SUV and Gleason score and Prostate-specific antigen (PSA) were performed. Kinetic modelling was performed and time-activity curves of healthy tissue and tumor tissue fitted and compared. Tumor kinetic parameters were normalized to those of healthy tissue producing ratios of K1 and k2. Median SUV in primary PCa was higher in high-grade compared to low-grade PCa (P = 0.052). No correlation was seen between Gleason score and SUV (P = 0.28). A trend-level correlation was seen between PSA and SUV (P = 0.078). Median SUV was 7.7 (4.7-22.5) for suspected lymph node metastases and 8.2 (5.4-14.8) for suspected bone metastases. A significant difference was seen between time-activity tissue curves for low- and high-grade PCa (P = 0.012). Highly significant differences were seen in K1- and k2-ratios between low- and high-grade PCa (P = 0.0006 and P < 0.0001). We showed that C-donepezil accumulates in primary PCa and metastases. Simple SUV values of the cancer hot spots were higher in high-risk tumors compared to low-risk tumors. Further studies should elucidate the importance of cholinergic neurogenesis for prostate cancer biology.