Julien Detour1,2, Alice Pierre1,2, Fréderic Boisson3, Guillaume Kreutter4,5, Thomas Lavaux6, Izzie Jacques Namer2,5,7, Laurence Kessler4,5,8, David Brasse3, Patrice Marchand3, Alessio Imperiale9,3,5,7. 1. Department of Radiopharmacy, Strasbourg University Hospitals, Strasbourg, France. 2. Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France. 3. Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France. 4. EA7293, Vascular and Tissular Stress in Transplantation, Illkirch, France. 5. Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France. 6. Department of Biochemistry and Molecular Biology, Strasbourg University Hospitals, Strasbourg, France. 7. ICube, CNRS/UMR7357, Strasbourg University, Strasbourg, France; and. 8. Department of Diabetology, Strasbourg University Hospitals, Strasbourg, France. 9. Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France alessio.imperiale@chru-strasbourg.fr.
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. METHODS: 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. RESULTS: 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. 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.
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. METHODS: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. RESULTS: 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. 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.
Authors: Benjamin Leroy-Freschini; Vincent Amodru; Pietro Addeo; Frédéric Sebag; Michel Vix; Laurent Brunaud; Marc Klein; Thibault Bahougne; Philippe Bachellier; Frédéric Castinetti; Bernard Goichot; Elodie Chevalier; David Taieb; Alessio Imperiale Journal: Eur J Nucl Med Mol Imaging Date: 2019-01-07 Impact factor: 9.236