Synthesis and bioevaluation of radioiodinated nitroimidazole hypoxia imaging agents by one-pot click reaction |
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| Institution: | 1. Department of Biological Sciences, California State University Los Angeles, Los Angeles, CA 90032, USA;2. Department of Chemistry and Biochemistry, California State University East Bay, Hayward, CA 94542, USA;3. Department of Chemistry and Biochemistry, California State University Los Angeles, Los Angeles, CA 90032, USA;1. Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;2. Merck & Co., Inc., 770 Sumneytown Pike, West Point, PA 19486, USA;1. Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, 11560 University Avenue Edmonton, Alberta, T6G 1Z2, Canada;2. Joint Appointment to Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2E1, Canada |
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| Abstract: | Eight radioiodinated 2-nitroimidazole derivatives for use as hypoxia imaging agents were synthesized by one-pot click reaction using four azides, two alkynes, and 131I]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, 131I]15 (131I]-(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 131I]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 131I]15 was a potential hypoxia imaging agent. |
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| Keywords: | Radioiodination 2-Nitroimidazole Hypoxia imaging agent Click reaction |
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