Novel ether-containing ligands as potential 99mtechnetium(I) heart agents

A novel pair of lipophilic cationic technetium complexes utilizing the 99mTc-tricarbonyl core have been developed and evaluated for cardiac uptake. Di-(pyridyl-2-methyl)amine (DPA) and di-(imidazol-2-ylmethyl)amine (DIA) ligands were functionalized using aliphatic or aromatic ether substituents to provide the ligands 3 and 4. Octahedral complexes with the fac {99mTc(CO)3(ligand)}+ configuration were readily formed by reaction of 99m[Tc(CO)3(H2O)3]+ with the ether-containing tridentate ligands. The 99mTc-tricarbonyl complexes, formed in >90% RCY and >90% RCP, were stable to transchelation in vitro against molar excesses of cysteine and histidine. Preliminary evaluation in rats after intravenous administration showed that the complexes concentrated in the heart muscle to an extent greater than surrounding tissue and blood. The 99mTc-complex with derivatized DIA, {99mTc(CO)3(4)}+ (8), demonstrated 1.8% ID/g in the heart and a 90:1 heart to blood ratio at 120 min post-injection. These initial results provide support for an expanded evaluation of novel cationic 99mTc-complexes for cardiac imaging.