Pharmacokinetics and Biodistribution of 99mTc N-MPO in Healthy Human Volunteers

Abstract

Tc N-MPO ([Tc N(MPO)(PNP5)]: HMPO = 2-mercaptopyridine N-oxide, and PNP5 = N-ethoxyethyl-N,N-bis[2-(bis(3-methoxypropyl)phosphino)ethyl]amine) is a new Tc radiotracer useful for myocardial perfusion imaging. This study was designed to determine its pharmacokinetics and biodistribution in healthy volunteers. Ten healthy volunteers were involved in this study. Each subject was administered approximately 925 MBq of Tc N-MPO under rest or stress conditions (n = 5 per group). Whole-body planar images were obtained at 10, 30, 60, 240, and 1440 minutes after injection. Organ uptake was quantified by region-of-interest analysis. The blood clearance and urine excretion kinetics were determined by collecting blood and urine samples at different time points. Tc N-MPO showed significant accumulation in myocardium with prolonged retention. At rest, its percentage of injected dose (%ID) uptake in the heart, lungs, and liver at 10 minutes after injection was 2.47% (0.64%), 1.84% (0.64%), and 20.88% (5.23%), respectively. The liver uptake decreased to 6.79%ID (1.60%ID) at 60 minutes after injection and 4.50%ID (1.86%ID) at 240 minutes after injection. Under stress conditions, the heart uptake was slightly increased (2.57%ID [0.21%ID]). The rapid liver clearance led to favorable heart-to-liver ratios, reaching values of 0.27%ID (0.07%ID) under rest condition and 0.28%ID (0.05%ID) under stress condition at 60 minutes after injection. Tc N-MPO demonstrates a highly favorable biodistribution in humans. The high heart uptake and the fast liver washout of Tc N-MPO will allow SPECT images of the left ventricle to be acquired as early as 10 minutes after injection.