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.