Evaluation of a Novel 18 F-Labeled Positron-Emission Tomography Perfusion Tracer for the Assessment of Myocardial Infarct Size in Rats

Author:

Sherif Hossam M.1,Saraste Antti1,Weidl Eliane1,Weber Axel W.1,Higuchi Takahiro1,Reder Sybille1,Poethko Thorsten1,Henriksen Gjermund1,Casebier David1,Robinson Simon1,Wester Hans-Jürgen1,Nekolla Stephan G.1,Schwaiger Markus1

Affiliation:

1. From the Department of Nuclear Medicine (H.M.S., A.S., E.W., A.W.W., T.H., S.R., T.P., G.H., H.J.W., S.G.N., M.S.), Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; Departments of Discovery Chemistry and Discovery Biology (D.C., S.R.), Lantheus Medical Imaging, North Billerica, Mass; and Tōkai Pharmaceutical Company, Cambridge, Mass.

Abstract

Background— The goal of this study was to evaluate a new 18 F-labeled positron-emission tomography (PET) perfusion tracer, 18 F BMS747158-02, for the assessment of myocardial infarct (MI) size. Methods and Results— Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of 18 F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of 18 F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent ( r =0.88; P <0.01; mean difference, 1.86%) or transient ( r =0.92; P <0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size ( r =−0.81; P <0.01; n=23). Conclusions— Myocardial 18 F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine,Radiology, Nuclear Medicine and imaging

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