Biological in Vitro and in Vivo Studies of a Series of New Asymmetrical Cationic [99mTc(N)(DTC-Ln)(PNP)]+ Complex (DTC-Ln = Alicyclic Dithiocarbamate and PNP = Diphosphinoamine)

99mTc(N)-DBODC5 is a cationic mixed compound under clinical investigation as potential myocardial imaging agent. In spite of this, analogously to the other cationic 99mTc-agents, presents a relatively low first-pass extraction. Thus, modification of 99mTc(N)-DBODC(5) direct to increase its first-pass extraction keeping unaltered the favorable imaging properties would be desirable. This work describes the synthesis and biological evaluation of a series of novel cationic 99mTc-nitrido complexes, of general formula [99mTcN(DTC-Ln)(PNP)]+ (DTC-Ln= alicyclic dithiocarbamates; PNP = diphosphinoamine), as potential radiotracers for myocardial perfusion imaging. The synthesis of cationic 99mTc-(N)-complexes were accomplished in two steps. Biodistribution studies were performed in rats and compared with the distribution profiles of 99mTc(N)-DBODC5 and 99mTc-Sestamibi. The metabolisms of the most promising compounds were evaluated by HPLC methods. Biological studies revealed that most of the complexes have a high i...