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(Circulation. 1997;95:1577-1584.)
© 1997 American Heart Association, Inc.

Articles

Very Early Noninvasive Detection of Acute Experimental Nonreperfused Myocardial Infarction With ^99mTc-Labeled Glucarate

Presented for the Young Investigator Award of the Cardiovascular Council in the 41st Annual Meeting of the Society of Nuclear Medicine, June 5, 1994, Orlando, Fla.

Jagat Narula; Artiom Petrov; Koon-Yan Pak; Bradford C. Lister; Ban-An Khaw

From the Center for Drug Targeting and Analysis (J.N., A.P., B.C.L., B.-A.K.), Northeastern University, Boston, Mass; Cardiac Unit (J.N., B.-A.K.), Massachusetts General Hospital and Harvard Medical School, Boston, Mass; and Molecular Targeting Technologies Inc (K.-Y.P., B.-A.K.), Malvern, Pa.

Correspondence to Ban-An Khaw, PhD, George D. Behrakis Professor of Pharmaceutical Sciences, Center for Drug Targeting and Analysis, 205 Mugar, Northeastern University, Boston, MA 02115.

Background ^99mTc glucarate has recently been reported to be an infarct-avid agent. The feasibility of imaging with ^99mTc glucarate was evaluated for the early diagnosis of nonreperfused and reperfused myocardial infarction and compared with localization of simultaneously administered ¹¹¹In anti-myosin.

Methods and Results Four groups of six rabbits each were studied. The left anterior descending coronary artery (LAD) was kept persistently occluded (n=6) or reperfused after 40 minutes (n=6) in rabbits. After confirmation of LAD occlusion by ²⁰¹Tl scintigraphy, a mixture of ^99mTc glucarate (15.7±1.6 mCi) and ¹¹¹In anti-myosin (0.53±0.03 mCi) was administered intravenously. Another group of rabbits (n=6) with 5 or 15 minutes of LAD occlusion were used to assess the affinity of ^99mTc glucarate for the ischemic myocardium. The remaining 6 rabbits with reperfused myocardial infarction were used for the assessment of subcellular localization of ^99mTc glucarate. ^99mTc glucarate cleared rapidly from circulation (elimination t_1/2, 36 minutes). Infarcts were visualized within 10 minutes in reperfused and within 30 minutes in nonreperfused coronary territories after intravenous administration. ¹¹¹In anti-myosin delineated reperfused infarcts within 1 to 3 hours, but no uptake was seen in persistently occluded rabbits. ^99mTc glucarate uptake in reperfused and nonreperfused infarct centers was 28 and 12 times greater, respectively, than that in normal myocardium (P=.0001). A direct correlation between glucarate and anti-myosin localization (r=.60 for nonreperfused; 0.76 for reperfused; P<.0001) was observed. Ischemic hearts showed no glucarate uptake. Subcellularly, ^99mTc glucarate localized predominantly in the nuclear fraction of the infarct, with lesser extents in the mitochondrial and cytoplasmic fractions.

Conclusions Noninvasive imaging of myocardial infarcts with ^99mTc glucarate is possible within minutes in persistently occluded or reperfused myocardial infarcts. Early detectability results from the rapid blood clearance and high avidity of glucarate for the acutely necrotic myocardial tissue.

Key Words: myocardial infarction • imaging • antibodies • coronary disease • myosin • reperfusion

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