Early detection of infarct in reperfused canine myocardium using 99mTc-glucarate.
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).


CONCLUSIONS
(99m)Tc-Glucarate marks acute myocardial infarct very early after occlusion and appears to accurately assess infarct size when compared with TTC staining.
Okada
David R
DR
Department of Biology, University of Tulsa, Tulsa, Oklahoma, USA. rokada576@hotmail.com
Johnson
Gerald
G
Liu
Zhonglin
Z
Hocherman
Sonia D
SD
Khaw
Ban-An
BA
Okada
Robert D
RD
D000818:Animals; D001783:Blood Flow Velocity; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D009203:Myocardial Infarction / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000601:surgery; D015425:Myocardial Reperfusion / Q000379:methods; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics*; D011237:Predictive Value of Tests; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics
D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C067171:technetium Tc 99m glucarate; D003402:Creatine Kinase; D005937:Glucaric Acid