TC-99M RADIOLABELED OUABAGENIN-CYSTEINE CONJUGATE - BIOLOGICAL EVALUATION IN ANIMAL-MODELS

Two ouabagenin-cysteine conjugates were synthesized by condensing 3-be ta monochloroacetyl and 3-beta, 11-alpha dichloroacetyl ouabagenin wit h cysteine. The resulting ligands were radiolabeled with technetium 99 m (Tc-99m) to furnish a single homogeneous Tc-99m chelate in each case with good stability. The animal experiments with these Tc-99m-labeled conjugates established the superiority of guinea pig over rat and rab bit as an animal model, as previously observed for other tritiated or radioiodinated cardiac glycosides or aglycones. In biodistribution exp eriments in guinea pig, these Tc-99m chelates showed a favorable heart to liver (and other nontarget organ) uptake ratio, comparable to that of recently reported I-125-digoxigenin iodohistamine-3-oxime, The low heart to blood ratio in animal experiments with ouabagenin derivative s could be attributed to the absence of 3-beta sugar residues in these molecules, which is in agreement with the previous observation report ed in connection with radioiodinated digoxin and digoxigenin derivativ es.