Assessment of myocardial inflammation produced by experimental coronary occlusion and reperfusion with Tc-99m-RP517, a new leukotriene B4 receptor antagonist that preferentially labels neutrophils in vivo

Article

关键词: POLYMORPHONUCLEAR LEUKOCYTES;    MYELOPEROXIDASE ACTIVITY;    ISCHEMIA-REPERFUSION;    INFARCTION;    ACCUMULATION;    BLOOD;    INFECTION;    MECHANISM;   

DOI  :  10.1161/01.CIR.0000023878.04716.6D

来源: SCIE

【 摘 要 】

Background-Tc-99m-RP517 is a new leukotriene B-4 (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of Tc-99m-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative Tc-99m-RP517 binding to human leukocyte subtypes and the Tc-99m-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor alpha (TNFalpha) 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 Tc-99m-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. Tc-99m-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlusion (90 minutes) and reperfusion (120 minutes) (n=9) or before intramyocardial TNFalpha injection (n=3). Ex vivo images of heart spices were acquired. The left ventricle was divided into 72 segments for flow and Tc-99m-RP517 uptake analysis. There was an inverse exponential relationship between Tc-99m-RP517 uptake and occlusion flow (r=0.73). In the same 15 segments, Tc-99m-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, Tc-99m-RP517 uptake correlated with myeloperoxidase and was observed on ex vivo images. indicating that this tracer may have potential as an inflammation-imaging agent.

【 授权许可】

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