Mechanism for myocardial localization and rapid liver clearance of Tc-99m-N-MPO: A new perfusion radiotracer for heart imaging

[Tc-99m-N(mpo)(PNP5)](+) (Tc-99m-N-MPO: Hmpo = 2-mercaptopyridine N-oxide and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc-99m radiotracer useful for myocardial perfusion imaging. The main objective of this study is to elucidate the mechanism for myocardial localization and fast liver clearance of Tc-99m-N-MPO in comparison with Tc-99m-sestamibi ([Tc-99m-(MIBI)(6)](+): MIBI = 2-methoxy-2-methylpropylisonitrile). Subcellular distribution of Tc-99m-N-MPO and Tc-99m-sestamibi was examined in the excised Sprague-Dawley (SD) rat myocardium. Biodistribution and planar imaging studies were performed using SD rats in the absence/presence of Cyclosporin-A. Due to negative plasma and mitochondrial potentials, 84.5% +/- A 3.2% of Tc-99m-N-MPO was found in the mitochondrial fraction as compared to 88.0% +/- A 1.5% of Tc-99m-sestamibi. There was no significant difference in their mitochondrial accumulation. Tc-99m-N-MPO was also able to retain its chemical integrity in rat myocardium. Pre-treatment of SD rats with Cys-A result in significant increase in the kidney and liver uptake of Tc-99m-N-MPO. Tc-99m-N-MPO and Tc-99m-sestamibi share almost identical subcellular distribution and localization mechanism. The MDR transport function of hepatocytes and renal cells is responsible for the fast clearance kinetics of Tc-99m-N-MPO from liver and kidneys, respectively. Tc-99m-N-MPO is a very promising myocardial perfusion radiotracer with favorable biodistribution properties and rapid liver clearance.