The RET (rearranged-during-transfection protein) protooncogene triggers multiple intracellular signaling cascades regulating cell cycle progression and cellular metabolism. We therefore hypothesized that metabolic imaging could allow noninvasive detection of response to the RET inhibitor vandetanib in vivo. Methods: The effects of vandetanib treatment on the fullgenome expression and the metabolic profile were analyzed in the human medullary thyroid cancer cell line TT. In vitro, transcriptional changes of pathways regulating cell cycle progression and glucose, dopa, and thymidine metabolism were correlated to the results of cell cycle analysis and the uptake of 3H-deoxyglucose, 3H-3,4-dihydroxy-L-phenylalanine, and 3H-thymidine under vandetanib treatment. In vivo, the tumor metabolism under vandetanib was monitored by small-animal PET of tumor-bearing mice. Results: Vandetanib treatmen
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