Synthesis and in vivo testing of a bromobutyl substituted 1,2-dithia-5,9-diazacycloundecane: a versatile precursor for new 99mTc-bis(aminoethanethiol) complexes.

7-(4'-Bromobutyl)-3,3,11,11-tetramethyl-1,2-dithia-5,9-di azacycloundecane (6) an intermediate for the preparation of new 99mTc-bis(aminoethanethiol) complexes (99mTc-BAT) was synthesized from the corresponding 7-(4'-phenoxybutyl) derivative (5) by ether cleavage with HBr/AcOH. To demonstrate its versatility as an alkylating agent, 6 was reacted with the amines piperidine, morpholine, NH3 and 1-phenyl-1,3,8-triazaspiro(4,5)decan-4-one, yielding the corresponding N-alkylated amines. Mild ring opening affording the BAT-ligands was achieved by reductive cleavage of the disulphide bonds with threo-2,3-dihydroxy-1,4-dimercaptobutane. The 99mTc-BAT complexes prepared by the tin-reduction method proved to be stable under in vitro conditions. With the exception of the 7-(4'-aminobutyl) substituted one, the 99mTc-BAT complexes revealed octanol-buffer partition coefficients (P) of P greater than 1 at physiological pH. The complexes proved to be neutral and the amount of ultrafiltrable 99mTc-BAT complex varied between 8-18%. In contrast to the good in vitro characteristics, the brain uptake values in CD-1 mice were comparably low.