Studies of the myocardial uptake and excretion mechanisms of a novel 99mTc heart perfusion agent

Introduction99mTc-TMEOP is a novel heart perfusion radiotracer exhibiting high initial and persistent heart uptake associated with rapid blood and liver clearance. This study aimed at determining the mechanisms of myocardial localization and fast liver clearance of 99mTc-TMEOP.MethodsSubcellular distribution of 99mTc-TMEOP was determined in excised rat heart tissue by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of 99mTc-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies.ResultsSubcellular distribution studies showed that more than 73% of 99mTc-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of 99mTc-sestamibi showed no significant difference in the mitochondrial accumulation between the two tracers. Biodistribution studies in the presence of cyclosporin A revealed an increase in kidneys and liver uptake of 99mTc-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile.ConclusionsThe heart uptake mechanism of 99mTc-TMEOP is similar to that of the other reported monocationic 99mTc cardiac agents and is associated with its accumulation in the mitochondria. Cyclosporin A studies indicate that the fast liver and kidney clearance kinetics is mediated by P-glycoprotein (Pgp), supporting the potential interest of this radiotracer for imaging Pgp function associated with multidrug-resistant tumours.