| 16891117 |
Zhou D, Chu W, Rothfuss J, Zeng C, Xu J, Jones L, Welch MJ, Mach RH: Synthesis, radiolabeling, and in vivo evaluation of an 18F-labeled isatin analog for imaging caspase-3 activation in apoptosis. Bioorg Med Chem Lett. 2006 Oct 1;16(19):5041-6. Epub 2006 Aug 7.
A non-peptide-based isatin sulfonamide analog, WC-II-89, was synthesized and its inhibition toward recombinant human caspase-3 and other caspases was determined. This compound showed high potency for inhibiting caspase-3 and -7, and high selectivity against caspases-1, -6, and -8. [(18) F] WC-II-89 was synthesized via a nucleophilic substitution of the corresponding mesylate precursor in high yield and radiochemical purity. Biodistribution studies using [(18) F] WC-II-89 revealed higher uptake in liver and spleen of cycloheximide-treated rats, an animal model of apoptosis, relative to control animals. Western blot analysis confirmed the presence of activated caspase-3 in the liver and spleen of cycloheximide-treated animals. MicroPET imaging studies revealed a high uptake of the radiotracer in the liver of a cycloheximide-treated rat relative to the untreated control. These data suggest that [(18) F] WC-II-89 is a potential radiotracer for imaging caspase-3 activation in tissues undergoing apoptosis. |
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