99mTc-DADT complexes substituted with heterocyclic amines: effect of substitution on in vivo reactivity

Alkylpiperidinyl and alkylpyrrolidinyl 99mTc-DADT complexes were synthesized and tested for their ability to cross the BBB. Each complex was a mixture of two epimers separated by HPLC. More lipophilic epimers were biologically evaluated in mice, at various time intervals. Similar biodistribution patterns were obtained for both piperidinyl and pyrrolidinyl DADT-complexes. Brain uptake or retention was influenced by the heterocyclic amine introduced into the DADT backbone. Subcellular concentration of selected 99mTc-DADT complexes was more profound in crude nuclear and post-microsomal fractions. Moreover, interaction of 99mTc-2,2,6,6,9,9-hexamethyl-4,7-diaza-4-(3-methylpyrroli dinyl)-ethyl-1,10- decanedithiol with either lipids or microsomes of whole brain was almost unaffected by time. This may suggest that a possible selective site of interaction and metabolism for DADT complexes occurs in brain.