Reactions of methyl, hydroxyl and peroxyl radicals with the DOTA chelating agent used in medical imaging

The mechanism of reaction of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) with ·CH₃, CH₃O₂· and ·OH radicals were studied. The radicals were formed in situ radiolytically. The methyl radicals react orders of magnitude slower with DOTA and with M^III(DOTA)^- than the hydroxyl radicals. The various final products were identified and mechanisms for their formation are proposed. CH₃O₂· radicals do not react, or react too slowly to be observed, with DOTA and with M^III(DOTA)^- as long as the central cation is not oxidized by the peroxyl radical. The results imply that synthesis of the M^III(DOTA)^-(M^III = radioisotope) complexes in a water-organic solvent (ethanol or 2-propanol or acetonitrile) mixture is not only kinetically desired but the so formed complex also decreases the radiolytic decomposition of DOTA.