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  • Title: Studies of the myocardial uptake and excretion mechanisms of a novel 99mTc heart perfusion agent.
    Author: Mendes F, Gano L, Fernandes C, Paulo A, Santos I.
    Journal: Nucl Med Biol; 2012 Feb; 39(2):207-13. PubMed ID: 22079035.
    Abstract:
    INTRODUCTION: (99m)Tc-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 (99m)Tc-TMEOP. METHODS: Subcellular distribution of (99m)Tc-TMEOP was determined in excised rat heart tissue by differential centrifugation. The effect of cyclosporin A on the pharmacokinetic behaviour of (99m)Tc-TMEOP was evaluated by both ex vivo biodistribution and in vivo planar imaging studies. RESULTS: Subcellular distribution studies showed that more than 73% of (99m)Tc-TMEOP was associated with the mitochondrial fraction. Comparison with subcellular distribution of (99m)Tc-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 (99m)Tc-TMEOP, suggesting the involvement of multidrug resistance transporters in determining its pharmacokinetic profile. CONCLUSIONS: The heart uptake mechanism of (99m)Tc-TMEOP is similar to that of the other reported monocationic (99m)Tc 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.
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