Effects of Recombinant Human Thyroid-Stimulating Hormone Superagonists on Thyroidal Uptake of 18F-Fluorodeoxyglucose and Radioiodide

Background: Superagonist analogs of human thyroid-stimulating hormone (hTSH) may stimulate the uptake of 131 I-iodide and 18 F-fluorodeoxyglucose ( 18 F-FDG) in thyroid carcinomas to a greater degree than hTSH. We herein report the potency and efficacy of two hTSH analogs, TR1401 and TR1402, to stimulate radioiodide and 18 F-FDG uptake in FRTL-5 cells and compared the effects of hTSH and TR1401 on radioiodide uptake in the thyroid in vivo in mice. Methods: The effects of hTSH analogs on intracellular levels of cAMP, uptake of 131 I-iodide, and 18 F-FDG were studied in FRTL-5 cells to determine the stimulatory potency and efficacy of the compounds by calculating half-maximum effective concentration (EC 50 ) values and maximal stimulatory effects (E max ). Biodistribution studies ( n = 96) and positron emission tomography/computed tomography imaging studies (single animals) on thyroid 125 I/ 124 I-iodide uptake were performed with T3-suppressed CD-1 mice in a dose-dependent manner (3, 10, and 30 μg/animal). Results: The EC 50 values of TR1401 and TR1402 demonstrated a 90-fold or 800-fold higher potency for their capacity to increase intracellular cAMP levels in comparison with hTSH ( p