Synthesis, Radiosynthesis, and in vitro Studies on Novel Hypoxia PET Tracers Incorporating [ 18 F]FDR

We report the synthesis of five radiotracers incorporating different oxyamine spacers between hypoxia-reactive 2-nitroimidazole moiety and 5-[18F]-fluorodeoxyribose ([18F]FDR, 12) prosthetic group: three linear alkyl chains with 3, 5, 7 carbon atoms (15 a–c), a cyclopropyl ring d) 1,4-disubstituted-1,2,3-triazole e). Experiments in hypoxic cells showed that 15 d displays superior uptake kinetics – similar selectivity for relative to gold standard hypoxia tracers [18F]fluoroazomycin arabinoside ([18F]FAZA) [18F]fluoromisonidazole ([18F]FMISO). Lipophilicity structural rigidity have strong influence on towards cells: lead tracer logP=0.38 most rigid spacer. A sixth radiotracer f), 2-H-imidazole replacing d, was used demonstrate group does not play meaningful role sensitivity hypoxia.