CLEARANCE OF TECHNETIUM 99M N-NOET IN NORMAL, ISCHEMIC-REPERFUSED, AND MEMBRANE-DISRUPTED MYOCARDIUM

Background, Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbama to) nitrido technetium(v) ((TcN)-Tc-99m-NOET) is a new neutral cardiac perfusion imaging agent that has been shown to have very high uptake and retention in vitro, The purpose of this study was to determine the clearance kinetics of (TcN)-Tc-99m-NOET in control, ischemic-reperfus ed, and membrane-disrupted myocardium. Methods and Results, After a 10 0 mu Ci (3.7 x 10(6) Po) bolus of (TcN)-Tc-99m-NOET was injected, myoc ardial clearance was monitored for 1 hour by the use of a sodium iodid e detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts, S even hearts were used as controls (group 1), In seven ischemic-reperfu sed hearts, tracer administration and uptake was followed by 30 minute s of no flow and 1 hour of reflow (group 2), In six additional ischemi c-reperfused hearts, tracer administration was followed by deprivation of flow for 1 hour followed by 1 hour of reflow (group 3), Six hearts were perfused,vith a 0.5% Triton X-100 KH perfusate for 1 hour (group 4), Four hearts were perfused with KH for 10 minutes, followed by cya nide for 10 minutes (group 5), This cycle was repeated three times, Ac tivities remaining in each heart at the end of each experiment were qu antitated, and activity at peak uptake was calculated, The (TcN)-Tc-99 m-NOET myocardial clearance was near linear in the control (0.6 +/- 0. 4) and both ischemic-reperfused groups with virtually no fractional cl earance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS), In th e Triton X-100 membrane-disrupted hearts, clearance was substantial (9 4.2% +/- 4.0%; p < 0.0001 compared with the control and ischemic-reper fused groups), Cyanide treatment produced rapid clearance, which was a rrested by a return to the standard KH perfusate, Peak uptake as a per centage of injected dose was 74.9% +/- 1.4% for all groups combined, C onclusion, Thus (TcN)-Tc-99m-NOET has extremely high myocardial retent ion after 1 hour in normal myocardium and is not significantly affecte d by ongoing myocardial ischemia or reperfusion injury in this model, Clearance is increased markedly in extreme conditions of membrane disr uption, These data are consistent with the concept that Tc-99m-NOET is localized predominantly in or on cell membranes, (TcN)-Tc-99m-NOET is a promising, new myocardial perfusion imaging agent that exhibits a s table myocardial distribution in the setting of acute developing injur y.