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 β-cells and an insulinoma xenograft model in mice. ¹⁸F-FDOPA in vitro accumulation was assessed in the murine β-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. Incubation of RIN-m5F cells with 80 μM carbidopa 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. 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.