99mTc-Glucarate is an infarct-avid imaging agent with the potential for very early detection of myocardial infarction. The purposes of this study using a canine model were to determine (a) the time course of (99m)Tc-glucarate uptake and clearance from necrotic and normal myocardium; (b) the (99m)Tc-glucarate necrotic-to-normal activity ratio over time; (c) the time course of detectable scan positivity after intravenous administration of the tracer; and (d) the relationship of infarct size determined by triphenyltetrazolium chloride (TTC) staining versus (99m)Tc-glucarate imaging ex vivo.
Methods: A 90-min left circumflex coronary artery (LCx) occlusion was followed by 270 min of reperfusion at 100% baseline flow in 6 open-chest, anesthetized dogs. (99m)Tc-Glucarate (555 MBq [15 mCi]) was injected 30 min after reperfusion and was followed by 240 min of gamma-camera serial imaging. Microspheres were injected during baseline, occlusion, tracer injection, and before the dogs were euthanized. Creatine kinase assays were performed to assess developing injury. Ex vivo gamma-camera imaging was performed. Blood flow and tracer activity were determined by well counting. TTC stain was used to mark infarct areas, which were sized using computerized digital planimetry.
Results: Hemodynamics demonstrated no significant change from baseline at any time for any parameter except LCx flow, which was significantly depressed during occlusion. The mean infarct size +/- SEM was 10.7% +/- 2% of total left ventricle. Blood (99m)Tc-glucarate clearance was triexponential and rapid. Qualitative image analysis revealed a well defined hot spot after 30 min, which remained well defined through 240 min after injection (150 and 360 min after occlusion, respectively). Images were quantitatively abnormal with hot spot-to-normal zone activity ratios of >/=2:1 within 10 min of tracer administration (130 min after occlusion), reaching 8:1 at 240 min after tracer administration (360 min after occlusion). There was a linear correlation between infarct size determined by (99m)Tc-glucarate and TTC staining (r = 0.96; slope = 0.87).
Conclusion: (99m)Tc-Glucarate marks acute myocardial infarct very early after occlusion and appears to accurately assess infarct size when compared with TTC staining.