Tc-99m-N-MPO: Novel cationic Tc-99m radiotracer for myocardial perfusion imaging

Abstract

Technetium 99m-N-MPO ([Tc-99m-N(mpo)(PNP5)](+)) is a cationic Tc-99m nitrido complex. The objective of this study is to evaluate its potential as a new radiotracer for myocardial perfusion imaging. Biodistribution studies were performed in Sprague-Dawley rats and guinea pigs to compare the myocardial uptake and excretion kinetics of Tc-99m-N-MPO from noncardiac organs, such as the liver and lungs, with those of the known cationic Tc-99m radiotracers: Tc-99m-N-DBODC5 and Tc-99m-sestamibi. Planar imaging was performed in Sprague-Dawley rats to evaluate the utility of Tc-99m-N-MPO as a myocardial perfusion imaging agent. Metabolism studies were carried out by use of both Sprague-Dawley rats and guinea pigs. In general, the heart uptake of Tc-99m-N-MPO was between that of Tc-99m-sestamibi and Tc-99m-N-DBODC5 over the 2-hour study period. However, the heart-liver ratio of Tc-99m-N-MPO (12.75 +/- 3.34) at 30 minutes after injection was more than twice that of Tc-99m-N-DBODC5 (6.01 +/- 1.45) and approximately 4 times higher than that of Tc-99m-sestamibi (2.90 +/- 0.22). The heart uptake and heart-liver ratio of Tc-99m-N-MPO and Tc-99m-sestamibi in guinea pigs were significantly lower than those obtained in Sprague-Dawley rats. The metabolism studies demonstrated no detectable Tc-99m-N-MPO metabolites in the urine and feces samples of the Sprague-Dawley rats at 120 minutes after injection. In guinea pigs no Tc-99m-N-MPO metabolites were detected in the urine at 120 minutes, but only approximately 60% of Tc-99m-N-MPO remained intact in the feces samples. In contrast, there was no intact Tc-99m-sestamibi detected in urine samples, and less than 15% of Tc-99m-sestamibi remained intact in the feces samples. Planar imaging studies indicated that clinically useful images of the heart may be obtained as early as 15 minutes after injection of Tc-99m-N-MPO. The combination of favorable organ biodistribution and myocardial uptake with rapid liver clearance makes Tc-99m-N-MPO a very promising myocardial perfusion radiotracer worthy of further evaluation in various preclinical animal models.