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Cardiovascular: Basic ScienceSmall Animal Imaging |
1 Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin
124
Objectives: 99mTc-Duramycin is a novel molecular probe for the targeted imaging of apoptotic and necrotic cells by binding to externalized phosphatidylethanolamine (PtdE). The goal is to quantify the uptake of 99mTc-Duramycin in infarcted and area-at-risk myocardium after ischemia and reperfusion, using a rat model of myocardial infarction.
Methods: Duramycin was labeled with 99mTc using HYNIC coordination chemistry. Acute myocardial infarction in rats was induced by ligating the left descending anterior coronary artery for 30 min, followed by reperfusion. 99mTc-Duramycin was injected via the tail vein at 2 hr after reperfusion. In vivo dynamic planar imaging was acquired using a gamma camera. At 1 hr after injection, the retention of 99mTc-Duramycin in the infarcted and ischemic non-infarct myocardium was determined by gamma counting of dissected tissues.
Results: In vivo imaging using 99mTc-Duramycin resulted in a highly conspicuous detection of the infarcted myocardium within 10 to 20 min after injection (Figure 1). Region of interest (ROI) analysis indicates that 99mTc-Duramycin rapidly accumulates in the infarcted myocardium. The level of binding in the infarcted heart persists without washout over time. Quantitatively, the radioactivity uptake in the infarcted, ischemic non-infarct and normal myocardium was 4.7 ± 0.6, 2.3 ± 0.2, and 0.15 ± 0.1%ID/g, respectively.
Conclusions: 99mTc-Duramycin accumulates avidly to infarct tissues, due to its tight binding with PtdE externalized in apoptotic and necrotic cells. For the early detection of myocardial infarction, 99mTc-Duramycin is particularly promising for its specificity, fast infarct binding, prompt blood clearance and low hepatic uptake.
Research Support: American Heart Association
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