Oxidation of p-[(125)I]Iodobenzoic Acid and p-[(211)At]Astatobenzoic Acid Derivatives and Evaluation In Vivo

The alpha particle-emitting radionuclide astatine-211 ((211)At) is of interest for targeted radiotherapy; however, low in vivo stability of many (211)At-labeled cancer-targeting molecules has limited its potential. As an alternative labeling method, we evaluated whether a specific type of astatinated aryl compound that has the At atom in a higher oxidation state might be stable to in vivo deastatination. In the research effort, para-iodobenzoic acid methyl ester and dPEG(4)-amino acid methyl ester derivatives were prepared as HPLC standards. The corresponding para-stannylbenzoic acid derivatives were also prepared and labeled with (125)I and (211)At. Oxidization of the [(125)I]iodo- and [(211)At]astato-benzamidyl-dPEG(4)-acid methyl ester derivatives provided materials for in vivo evaluation. A biodistribution was conducted in mice with coinjected oxidized (125)I- and (211)At-labeled compounds. The oxidized radioiodinated derivative was stable to in vivo deiodination, but unfortunately the oxidized [(211)At]astatinated benzamide derivative was found to be unstable under the conditions of isolation by radio-HPLC (post animal injection). Another biodistribution study in mice evaluated the tissue concentrations of coinjected [(211)At]NaAtO(3) and [(125)I]NaIO(3). Comparison of the tissue concentrations of the isolated material from the oxidized [(211)At]benzamide derivative with those of [(211)At]astatate indicated the species obtained after isolation was likely [(211)At]astatate.