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