^99mTc-glucarate kinetics differentiate normal, stunned, hibernating, and nonviable myocardium in a perfused rat heart model

Purpose ^99mTc-glucarate is an infarct-avid imaging agent. However, patients may have mixtures of normal, irreversibly injured, stunned, and hibernating myocardium. The purposes were to determine ^99mTc- glucarate uptake and clearance kinetics in these four conditions, and its ability to determine the extent of injury. Methods Twenty-two perfused rat hearts were studied: controls (n=5), stunned (n=5; 20-min no-flow followed by 5-min reflow), hibernating (n=6; 120-min low flow at 4 ml/min), and ischemic-reperfused (n=6; 120-min no-flow followed by reflow). ^99mTc-glucarate was then infused. Tracer activity was monitored using a NaI scintillation detector and a multichannel analyzer. Creatine kinase, electron microscopy, and triphenyltetrazolium chloride determined viability. Results ^99mTc-glucarate 10-min myocardial uptake was significantly greater in ischemic-reperfused (2.50±0.09) (cpm, SEM) than in control (1.74±0.07), stunned (1.68± 0.11), and hibernating (1.59±0.11) (p<0.05). Tracer retention curves for ischemic-reperfused were elevated at all time points as compared with the other groups. ^99mTc-glucarate 60-min myocardial uptake was significantly greater in ischemic-reperfused (7.60±0.63) than in control (1.98±0.15), stunned (1.79±0.08), and hibernating (2.33±0.15) (p<0.05). The 60-min well-counted tracer activity ratio of ischemic-reperfused to control was 9:1 and corroborated the NaI detector results. Creatine kinase, triphenyltetrazolium chloride, and electron microscopy all demonstrated significantly greater injury in ischemic-reperfused compared to the other groups. An excellent correlation was observed between viability markers and tracer activity (r=0.99 triphenylte-trazolium chloride; r=0.90 creatine kinase). Conclusion ^99mTc-glucarate activity continually and progressively increased in irreversibly injured myocardium. ^99mTc-glucarate uptake was strongly correlated with myocardial necrosis as determined by three independent assessments of viability. There were minimal and similar ^99mTc-glucarate uptakes in control, stunned, and hibernating myocardium.