Effects of no flow and reperfusion on technetium-99m-Q12 kinetics.

UNLABELLED: The purpose of this study were to determine if 99mTc-Q12 tracer kinetics could be affected by the insult of total no flow followed by reflow and the effects of viability on clearance. METHODS: In six control buffer perfused rat hearts, flow was maintained at 12 ml/min throughout uptake and clearance. In six hearts (IR30), 30 min of no flow was followed by 60 min of reflow. In six hearts (IR60), 60 min of no flow was followed by 60 min of reflow. One millicurie 99mTc-Q12 was injected in control hearts or during reflow in the IR30 and IR60 hearts and myocardial clearance was monitored for 1 hr using a Nal detector. RESULTS: Control hearts demonstrated biphasic 99mTc-Q12 myocardial clearance with an early rapid clearance phase ending 5-10 min after injection (73.5% +/- 1.5% retention) followed by a late slow clearance phase (90.5% +/- 0.2% retention). IR30 hearts demonstrated a near identical clearance curve (74.3% +/- 0.9% early retention, 90.9% +/- 0.6% late retention). IR30 heart electron micrographs demonstrated predominantly ischemia insulted but viable cells. IR60 hearts also demonstrated a biphasic myocardial clearance, with a late slow phase similar to controls (91.9% +/- 0.6% retention). The early rapid phase was significantly faster than controls (61.1% +/- 3.4%). IR60 heart electron micrographs demonstrated predominantly injured nonviable cells. Well counting confirmed decreased retention in the IR60 rats compared to controls and IR30 rats. CONCLUSION: Technetium-99m-Q12 myocardial clearance is normally biphasic, with an early rapid phase ending after 5-10 min and a late slow phase. Ischemicaly insulted but viable myocardium created by 30 min of no flow followed by reflow has no effect on either clearance phase. This tracer warrants further study to determine its potential utility in assessing myocardial viability.

Technetium 99m-Q12 kinetics in perfused rat myocardium: effects of hypoxia and low flow.

Technetium 99m-Q12 is a new cationic myocardial perfusion imaging agent that produces excellent images in human beings. The purpose of this study was to examine the separate effects of hypoxia and low flow on myocardial clearance kinetics. After a 1 mCi bolus injection, myocardial 99mTc-Q12 clearance was monitored for 1 hour by using an Nal detector in 24 isolated perfused rat hearts. In 6 control hearts, flow was 12 ml/min, and oxygenation was normal. In 6 hypoxic hearts, flow was normal, but oxygenation was reduced (<5% 02). In 6 low-flow hearts, flow was 3 ml/min, and oxygenation was normal. In 6 very low flow hearts, flow was 1 ml/min, and oxygenation was normal. 99mTc-Q12 myocardial clearance was biphasic in all four groups, consisting of a rapid early phase and a second slow phase that began after 10 minutes. Myocardial retention between 1 and 10 minutes was 56.8% +/- 1.8% for control, 49.2% +/- 2.2% (p < 0.05 compared with control) for hypoxic, 56.8% +/- 2.6% (p = NS compared with control) for low flow (3 ml/min), and 63.7% +/- 2.1 % (p < 0.05 compared with control) for very low flow hearts (1 ml/min). Myocardial retention between 10 and 60 minutes was 90.5% +/- 0.2% for control, 90.2% +/- 1.6% for hypoxic, 90.0% +/- 0.8% for low-flow hearts (3 ml/min), and 87.6% +/- 0.3% (p < 0.05 compared with other groups) for very low flow hearts (1 ml/min). In conclusion, 99mTc-012 demonstrates biphasic clearance from normal, hypoxic, low-flow, and very low flow ischemic myocardium. Early-phase myocardial retention is decreased by hypoxia and increased by very low flow.

Clearance of technetium 99m N-NOET in normal, ischemic-reperfused, and membrane-disrupted myocardium.

BACKGROUND: Technetium 99m-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) (99mTcN-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 99mTcN-NOET in control, ischemic-reperfused, and membrane-disrupted myocardium. METHODS AND RESULTS: After a 100 microCi (3.7 x 10(6) Bq) bolus of 99mTcN-NOET was injected, myocardial clearance was monitored for 1 hour by the use of a sodium iodide detector in 30 isolated, Krebs-Henseleit (KH) perfused rat hearts. Seven hearts were used as controls (group 1). In seven ischemic-reperfused hearts, tracer administration and uptake was followed by 30 minutes of no flow and 1 hour of reflow (group 2). In six additional ischemic-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 with a 0.5% Triton X-100 KH perfusate for 1 hour (group 4). Four hearts were perfused with KH for 10 minutes, followed by cyanide for 10 minutes (group 5). This cycle was repeated three times. Activities remaining in each heart at the end of each experiment were quantitated, and activity at peak uptake was calculated. The 99mTcN-NOET myocardial clearance was near linear in the control (0.6 +/- 0.4) and both ischemic-reperfused groups with virtually no fractional clearance (1.2% +/- 0.6% and 2.1% +/- 0.6%, respectively; p = NS). In the Triton X-100 membrane-disrupted hearts, clearance was substantial (94.2% +/- 4.0%; p < 0.0001 compared with the control and ischemic-reperfused groups). Cyanide treatment produced rapid clearance, which was arrested by a return to the standard KH perfusate. Peak uptake as a percentage of injected dose was 74.9% +/- 1.4% for all groups combined. CONCLUSION: Thus 99mTcN-NOET has extremely high myocardial retention after 1 hour in normal myocardium and is not significantly affected by ongoing myocardial ischemia or reperfusion injury in this model. Clearance is increased markedly in extreme conditions of membrane disruption. These data are consistent with the concept that 99mTc-NOET is localized predominantly in or on cell membranes. 99mTcN-NOET is a promising, new myocardial perfusion imaging agent that exhibits a stable myocardial distribution in the setting of acute developing injury.