Effect of Carbidopa on 18F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging.
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 on18F-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 of18F-FDOPA. Tumor xenografts were clearly detectable by small-animal PET in all cases. Insulinoma xenografts in carbidopa-treated mice showed significantly higher18F-FDOPA uptake than those in nontreated mice. Regardless of carbidopa premedication, the xenografts were characterized by an early increase in18F-FDOPA uptake and then a progressive reduction over time.


CONCLUSIONS
Carbidopa did not influence in vitro18F-FDOPA accumulation in RIN-m5F cells but improved insulinoma imaging in vivo. Our findings increase current knowledge about the18F-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.
Department of Radiopharmacy, Strasbourg University Hospitals, Strasbourg, France.|Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France.
Julien
J
Detour
Department of Radiopharmacy, Strasbourg University Hospitals, Strasbourg, France.|Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France.
Alice
A
Pierre
Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France.
Fréderic
F
Boisson
EA7293, Vascular and Tissular Stress in Transplantation, Illkirch, France.|Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France.
Guillaume
G
Kreutter
Department of Biochemistry and Molecular Biology, Strasbourg University Hospitals, Strasbourg, France.
Thomas
T
Lavaux
Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France.|Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France.|ICube, CNRS/UMR7357, Strasbourg University, Strasbourg, France; and.
Izzie Jacques
IJ
Namer
EA7293, Vascular and Tissular Stress in Transplantation, Illkirch, France.|Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France.|Department of Diabetology, Strasbourg University Hospitals, Strasbourg, France.
Laurence
L
Kessler
Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France.
David
D
Brasse
Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France.
Patrice
P
Marchand
Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg, France alessio.imperiale@chru-strasbourg.fr.|Institut Pluridisciplinaire Hubert Curien (IPHC), CNRS/UMR7178, Strasbourg University, Strasbourg, France.|Federation of Translational Medicine of Strasbourg (FMTS), Faculty of Medicine, Strasbourg University, Strasbourg, France.|ICube, CNRS/UMR7357, Strasbourg University, Strasbourg, France; and.
Alessio
A
Imperiale
D000818:Animals; D002230:Carbidopa / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D007089:Image Enhancement / Q000379:methods; D007340:Insulinoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D008657:Metabolic Clearance Rate / Q000187:drug effects; D008819:Mice, Nude; D009928:Organ Specificity / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution / Q000187:drug effects
D019275:Radiopharmaceuticals; C043437:fluorodopa F 18; D004295:Dihydroxyphenylalanine; D002230:Carbidopa
18F-FDOPA; PET; RIN-m5F; carbidopa; insulinoma; small-animal PET