Published online before print January 26, 2009, doi: 10.1161/CIRCIMAGING.108.815423
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Original Articles |
Evaluation of a Novel 18F-Labeled Positron-Emission Tomography Perfusion Tracer for the Assessment of Myocardial Infarct Size in Rats
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 T
kai Pharmaceutical Company, Cambridge, Mass.
Correspondence to Hossam M. Sherif, MD, Nuklearmedizinische Klinik der Technischen Universität München, Ismaningerstr 22, 81775 Munich, Germany. E-mail hossam_sherif_66{at}homail.com
Received August 23, 2008; accepted January 8, 2009.
Background— The goal of this study was to evaluate a new 18F-labeled positron-emission tomography (PET) perfusion tracer, 18F 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 18F 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 18F 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 18F 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.
Key Words: 18F BMS747158-02 • cardiac PET • perfusion • myocardial infarction • TTC staining
CLINICAL PERSPECTIVE
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