Effect of Carbidopa on 18F-FDOPA uptake in insulinoma: From cell culture to small-Animal PET Imaging

Abstract

Patient premedication with carbidopa seems to improve the accuracy of 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-FDOPA) PET for insulinoma diagnosis. However, the risk of PET false-negative results in the presence of carbidopa is a concern. Consequently, we aimed to evaluate the effect of carbidopa on 18F-FDOPA uptake in insulinoma b-cells and an insulinoma xenograft model in mice. Methods: 18F-FDOPA in vitro accumulation was assessed in the murine b-cell line RIN-m5F. In vivo small-Animal PET experiments were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F cells. Experiments were conducted with and without carbidopa pretreatment. Results: Incubation of RIN-m5F cells with 80 mMcarbidopa did not significantly affect the cellular accumulation of 18F-FDOPA. Tumor xenografts were clearly detectable by small-Animal PET in all cases. Insulinoma xenografts in carbidopa-Treated mice showed significantly higher 18F-FDOPA uptake than those in nontreated mice. Regardless of carbidopa premedication, the xenografts were characterized by an early increase in 18F-FDOPA uptake and then a progressive reduction over time. Conclusion: Carbidopa did not influence in vitro 18F-FDOPA accumulation in RIN-m5F cells but improved insulinoma imaging in vivo. Our findings increase current knowledge about the 18F-FDOPA uptake profile of RIN-m5F cells and a related xenograft model. To our knowledge, the present work represents the first preclinical research specifically focused on insulinomas, with potential translational implications.