O -(2- 18 F-fluoroethyl)- l -tyrosine ( 18 F-FET) uptake in insulinoma: first results from a xenograft mouse model and from human
Résumé
Introduction: Herein we have evaluated the uptake of O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) in insulinoma in
comparison with those of 6-18F-fluoro-3,4-dihydroxy-L-phenylalanine (18F-FDOPA) providing first data from
both murine xenograft model and one patient with proved endogenous hyperinsulinemic hypoglycemia.
Methods: Dynamic 18F-FET and carbidopa-assisted 18F-FDOPA PET were performed on tumor-bearing nude mice
after subcutaneous injection of RIN-m5Fmurine beta cells and on a 30-year-oldmanwith type-1 multiple endocrine
neoplasia and hyperinsulinemic hypoglycemia defined by a positive fasting test.
Results: Seven and three nude mice bearing a RIN-m5F insulinoma xenograft were respectively studied by 18FFET
and 18F-FDOPA μPET. Insulinoma xenograftwas detected in all the imaged animals. Xenograftwas characterized
by an early but moderate increase of 18F-FET uptake followed by a slight decline of uptake intensity during
the 20 min dynamic acquisition. Tumoral radiotracer peak intensity and the highest tumor-to-background contrast
were reached about 5 minutes after 18F-FET iv. injection (mean SUV: 1.21 ± 0.10). The biodistribution of
18F-FET and 18F-FDOPA and their dynamic tumoral uptake profile and intensitywere similar. In the examined patient,
18F-FDOPA and 18F-FET PET/CT showed one concordant focal area of well-defined increased uptake in the
pancreatic tail corresponding to 11 mm histologically proved insulinoma. The SUVmax tumor to liver ratio was
1.5, 1.1 for 18F-FDOPA, 1.1, 1 for 18F-FET at early (0-5 min post injection) and delayed (5-20 min post injection)
PET/CT acquisition, respectively. Despite the relatively low tumoral uptake intensity, insulinoma was clearly
identified due to the low background in the pancreas. At the contrary, no 18F-FDOPA or 18F-FET tumoral uptake
was revealed on whole-body PET/CT images performed about 30 min after radiotracer administration. Note of
worth, the dynamic uptake pattern of 18F-FET and 18F-FDOPA were similar between human insulinoma and
mice xenograft tumor.
Conclusion: 18F-FET PET compared equally to 18F-FDOPA PET in a preclinical RIN-m5F murine model of
insulinoma and in one patient with insulinoma-related hypoglycemia. However, in both cases, the tumoral uptake
intensity was moderate and the tumor was only visible until 20 min after radiotracer injection. Hence, caution
should be taken before asserting the translational relevance of our results in the clinical practices. However,
the structural analogies between 18F-FET and 18F-FDOPA as well as the limited pancreatic uptake of 18F-FET in
human, encourage evaluating 18F-FET as diagnostic radiotracer for insulinoma detection in further prospective
studies involving large cohorts of patients.