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(Circulation. 1998;97:2557-2566.)
© 1998 American Heart Association, Inc.

Basic Science Reports

^99mTc-HL91

"Hot Spot" Detection of Ischemic Myocardium In Vivo by Gamma Camera Imaging

Robert D. Okada, MD; Gerald Johnson, III, PhD; Kiem N. Nguyen, BS; Zhonglin Liu, MD; Barbara Edwards, BS; Colin M. Archer, PhD; Timothy L. North, BS; Adam C. King, PhD; ; James D. Kelly, PhD

From the William K. Warren Medical Research Institute of the University of Oklahoma Health Sciences Center, Tulsa (R.D.O., G.J., K.N.N., Z.L.), and Amersham International, Bucks, England (B.E., C.M.A., T.L.N., A.C.K., J.D.K.).

Correspondence to Gerald Johnson III, PhD, William K. Warren Medical Research Institute, 6465 S Yale, Suite 1010, Tulsa, OK 74136. E-mail gerald-johnson{at}uokhsc.edu

Background—^99mTc-HL91 is a new hypoxia imaging agent that demonstrates increased uptake and retention in globally hypoxic myocardium in vitro. The purpose of this study was to determine whether ^99mTc-HL91 could detect regional ischemia in vivo by gamma camera imaging.

Methods and Results—Eight open-chest dogs with left circumflex (LCx) stenoses were studied. Injection of 5 mCi of ^99mTc-HL91 and microspheres was followed by imaging over 4 hours. Heart slices were imaged, then stained with triphenyltetrazolium chloride (TTC), and tissues were well-counted. TTC staining demonstrated no injury. Mean LCx blood flow was 0.32±0.04 mL · min^-1 · g^-1, and mean left anterior descending coronary artery (LAD) flow was 0.96±0.02 mL · min^-1 · g^-1 (ratio, 0.33). "Hot spots" were detected in 8 of 8 experiments in vivo within 60 minutes and improved over 4 hours. Region of interest analysis of LCx/LAD activity ratios demonstrated significant increases within 30 minutes (final ratio, 3.0; P<0.05). LCx and LAD washout curves demonstrated significant differences within 15 minutes. Washout curves were biexponential over 1 hour, followed by linear retention from 1 to 4 hours. Four-hour fractional retention was 0.12 for LAD and 0.44 for LCx (P<0.01). Myocardial flow versus tracer uptake demonstrated 2 phases: phase 1 (flow, 0.05 to 0.7 mL · min^-1 · g^-1) had an inverse linear correlation (r=-0.80); phase 2, (flow, >0.7 mL · min^-1 · g^-1) had no correlation. Ischemic heart/liver ratios remained near 1.0 for 4 hours.

Conclusions—^99mTc-HL91 positively identifies regional myocardial ischemia in a canine model using ^99mTc imaging. Quantitative techniques allowed identification of ischemic myocardium within 15 minutes of tracer administration.

Key Words: imaging • hypoxia • technetium • ischemia • myocardium

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