Some aspects on the brain-retention mechanism for the complexation of Tc-99m and HMPAO in the presence of glutathione

The d,1- and meso-isomers of hexamethylpropyleneamine oxime (HM-PAO) can react with the pentavalent Tc-99m to give lipophilic complexes in which only the d,1-complex can be consistently retained in the brain. In order to get a better understanding about the Tc-99m HM-PAO retention mechanism in the brain, an in-vitro complexation study was carried out on the reduced Tc-99m species with HM-PAO at pH 7.0 and 37.0±0.2 deg C in the presence of glutathione at its brain-level concentration by means of radio-thin layer chromatography and paper electrophoresis. Both of the HM-PAO complexes as well as reduced Tc-99m species could react with the reduced form of glutathione to generate primarily negative charged species which were identified by paper electrophoresis . The d,1-HM-PAO complex was converted immediately, whereas the conversion rate for the meso-isomer complex was slower (Kd = 9.6 x 10-3 min-1) at 1 mM of glutathione concentration. The results indicate that the Tc-99m d,1-HM-PAO complex has longer brain-retention time than that of meso-isomer in their biodistribution studies. 10 refs., 5 figs