New bisaminoethanethiol (BAT) ligands which form two interconvertible Tc-99m complexes

Most commonly used radiopharmaceuticals in diagnostic nuclear medicine are labeled with Tc-99m. This is due to its superior physical characteristics (T1/2 = 6 h and gamma energy 140 KeV) and convenient availability from the 99Mo/99mTc generator. In an attempt to fine tune the properties of Tc-99m complexes, the synthesis and radiolabeling of two novel N2S2 ligands, N,-2-mercaptobenzyl-N'-(1-oxo-2-mercapto-2-methyl)propyl ethylene-diamine, 8, and N,-2-methylthiobenzyl-N'-(1-oxo-2-mercapto-2-methyl)propyl ethylenediamine, 11, with an ionizable SH or unionizable SMe group, respectively, for the formation of complexes with TcvO center cores, have been examined. Both ligands initially formed one apparently stable, lipophilic and neutral complex (HPLC, Rt = 7 min, reverse-phase column, acetonitrile: buffer, pH 7.0; 55/45; V/V; partition coefficient between 1-octanol and buffer of 410 and 335, respectively) with [99mTc]pertechnetate in the presence of stannous chloride. After treatment with a reducing agent, NaCNBH3, the initial [99mTc]8 and 11 complexes were reduced; the reduced complexes were less lipophilic (shorter retention time, Rt = 5 min, on the same reversed phase HPLC). However, only the oxidized form showed sufficient stability. The reduced forms of both [99mTc]8 and 11 were readily and completely converted back to the oxidized forms by a stream of air. Biodistribution studies in rats demonstrated that the [99mTc]8 (oxidized form) penetrated the blood-brain barrier (0.67% dose/organ at 2 min postinjection), but washed out from the brain quickly (0.29% dose/organ at 30 min postinjection).(ABSTRACT TRUNCATED AT 250 WORDS)