BIFUNCTIONAL CHELATOR FOR FACILE PREPARATION OF NEUTRAL TECHNETIUM COMPLEXES

The diaminedithiol (DADT) ligand system has proven to be useful as a c arrier of technetium-99m in the preparation of a wide variety of site- specific radiopharmaceuticals. To expand the utility of the ligand sys tem, we have designed and synthesized a bifunctional chelating agent b ased on the ligand system whose adducts generate a neutral technetium complex core and therfore can penetrate intact membranes. We have eval uated both the coupling of the thiolactone reactive moiety of the bifu nctional chelate to benzylamine as a model as well as subsequent label ing with technetium-99m. Reaction with benzylamine was complete at roo m temperature within 2 h, producing the adduct in 74 % isolated yield. On coordination of the benzylamine adduct to technetium-99m, one majo r product was obtained in high yield (>90%). The product was stable in serum and physiologic saline at 37-degrees-Cover a 20-h study period. The partition coefficient of the technetium complex was 101 +/- 6.2, indicating that the complex was lipophilic. Biodistribution studies in mice showed that the brain concentration at 5 min postinjection was 0 .91 +/- 0.09 % injected dose/g indicating that the complex penetrates the intact blood-brain barrier. This is further evidence that the comp lex is neutral and lipophilic. This bifunctional chelate should facili tate the incorporation of technetium-99m into molecules of biological interest such as drugs, small peptides, and metabolic substrates.