Synthesis and evaluation of [123I]-indomethacin derivatives as COX-2 targeted imaging agents

A novel series of iodinated indomethacin derivatives was synthesized, and evaluated as selective inhibitors of COX-2. Two candidate compounds N-(p-iodobenzyl)-2-(1-(p-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetamide (3) and 1-(p-iodobenzyl)-5-methoxy-2-methyl-3-indoleacetic acid (9) possessed optimum properties suitable for potential in vivo imaging. Arylstannane precursors for radioiododestannylation were synthesized in 70-85% yield from the iodo compounds by reaction with hexabutylditin and tetrakis(triphenylphosphine)palladium(0) in refluxing dioxane. Radioiododestannylation was conducted by reaction with carrier-added Na[I-123] in the presence of Chloramine-T in an EtOAc/H2O binary system under acidic conditions (pH 3.5), allowing direct isolation of the labeled products by separation of the organic phase. Radioiodinated products [I-123]3 and [I-123]9 Were recovered in a decay-corrected radiochemical yield of 86-87% and radiochemical purity of 98-99%.