Abstract 3733: Adenine nucleotide translocase2 mediates 18F-FDG uptake in dedifferentiated thyroid cancer

Objectives: 18F-fluorodeoxyglucose (FDG), an analogue of glucose, provides valuable functional information based on the increased glucose uptake and glycolysis in malignant tumor cells. Although both glucose transporter-1 (GLUT-1) and hexokinase2 (HK2) activity have been considered to associate with FDG uptake, the molecular mechanisms that determine FDG uptake are still largely unknown. Adenine nucleotide translocase 2 (ANT2) in the mitochondria inner membrane was reported to relate with tumor malignancy. We investigated the correlation between FDG uptake and Glut-1, HK2, and ANT2 expression in thyroid cancers throughout various spectrums of differentiation status. Methods: N-thy-ori (normal human thyroid cells), WRO (follicular cancer), BHP10-3 and TPC-1 (papillary cancer), and FRO (anaplastic cancer) were used for this research. GLUT-1, HK2, and ANT2 expressions were measured by western blot. ANT2 siRNAs and pcDNA3.1-ANT2 vectors were used to modify ANT2 expression. FDG uptakes were measured in thyroid cells and human embryonic kidney cells (293FT) with HK2 or ANT2 transfection. For patient tissue analysis, 95 thyroid tissue-array cores were evaluated, and which are classified 36 as normal, 44 as poorly differentiated (PD), and 15 as anaplastic thyroid cancer (ATC). ANT2 expression was measured by immunostaining, scored from 1 to 5. Results: FDG uptake in thyroid cancer cells was increased in anaplastic and poorly differentiated cells (P