Synthesis and bioevaluation of radioiodinated nitroimidazole hypoxia imaging agents by one-pot click reaction

Eight radioiodinated 2-nitroimidazole derivatives for use as hypoxia imaging agents were synthesized by one-pot click reaction using four azides, two alkynes, and [I-131]iodide ions and evaluated by hypoxic cellular uptake and biodistribution experiments. The results suggested that radiotracers with suitable partition coefficients (log P: -0.2-1.2) were more likely to have higher hypoxic cellular uptake. Among these eight molecules, [I-131]15 ([I-131]-(5-iodo-1-(2-(2-(2-nitro-1H-imidazol-1-yl)ethoxy)ethyl)-4-((2-nitro-1H-imidazol-1-yl)methyl)-1H-1,2,3-triazole)) had a suitable log P (0.05 +/- 0.03) and contained two 2-nitroimidazole groups. The hypoxic/aerobic cellular uptake ratio of [I-131]15 was 4.4 +/- 0.5, and the tumor/blood (T/B) and tumor/muscle (T/M) ratios were 2.03 +/- 0.45 and 6.82 +/- 1.70, respectively. These results suggested that [I-131]15 was a potential hypoxia imaging agent.