Published Online
on July 15, 2002

A more recent version of this article appeared on July 30, 2002

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Submitted on February 27, 2002
Revised on May 6, 2002
Accepted on May 6, 2002

Assessment of Myocardial Inflammation Produced by Experimental Coronary Occlusion and Reperfusion With ^99mTc-RP517, a New Leukotriene B4 Receptor Antagonist, That Preferentially Labels Neutrophils In Vivo

Laurent M. Riou PhD, Mirta Ruiz MD, Gail W. Sullivan MS, Joel Linden PhD, Howard Leong-Poi MD, Jonathan R. Lindner MD, Thomas D. Harris PhD, George A. Beller MD, and David K. Glover ME^*

From the University of Virginia Health System, Charlottesville, Va, and Bristol-Myers Squibb Medical Imaging (T.D.H.), N Billerica, Mass.

^* To whom correspondence should be addressed. E-mail: dglover{at}virginia.edu.

Background—^99mTc-RP517 is a new leukotriene B₄ (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of ^99mTc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative ^99mTc-RP517 binding to human leukocyte subtypes and the ^99mTc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor (TNF) injection.

Methods and Results—Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n=4) with a fluorescent analog of ^99mTc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added. ^99mTc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlusion (90 minutes) and reperfusion (120 minutes) (n=9) or before intramyocardial TNF injection (n=3). Ex vivo images of heart slices were acquired. The left ventricle was divided into 72 segments for flow and ^99mTc-RP517 uptake analysis. There was an inverse exponential relationship between ^99mTc-RP517 uptake and occlusion flow (r=0.73). In the same 15 segments, ^99mTc-RP517 uptake was highly correlated with the neutrophil enzyme myeloperoxidase (r=0.91). Ex vivo images revealed tracer uptake in the reperfused area (ischemic to normal count ratio=2.7±0.2).

Conclusions—RP517 binds to the neutrophil LTB4 receptor after intravenous injection. After reperfusion, ^99mTc-RP517 uptake correlated with myeloperoxidase and was observed on ex vivo images, indicating that this tracer may have potential as an inflammation-imaging agent.

Key words: inflammation • myocardium • imaging

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