TY - JOUR T1 - PET of Glucagonlike Peptide Receptor Upregulation After Myocardial Ischemia or Reperfusion Injury JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 1960 LP - 1968 DO - 10.2967/jnumed.112.109413 VL - 53 IS - 12 AU - Haokao Gao AU - Dale O. Kiesewetter AU - Xiaoxiang Zhang AU - Xinglu Huang AU - Ning Guo AU - Lixin Lang AU - Naoki Hida AU - Hui Wang AU - Haichang Wang AU - Feng Cao AU - Gang Niu AU - Xiaoyuan Chen Y1 - 2012/12/01 UR - http://jnm.snmjournals.org/content/53/12/1960.abstract N2 - Glucagonlike peptide (GLP-1) and its receptor (GLP-1R) exhibit cardioprotective effects after myocardial ischemia and reperfusion (MI/R) in both animal studies and clinical trials. However, the kinetics of GLP-1R expression in the infarcted/ischemic myocardium has not yet been explored. The purpose of this study was to monitor the presence and time course of regional myocardial GLP-1R expression after MI/R with noninvasive PET. Methods: Male Sprague–Dawley rats underwent a 45-min transient left coronary artery occlusion, followed by reperfusion. The myocardial infarction was confirmed by electrocardiogram and cardiac ultrasound. In vivo PET was performed to determine myocardial uptake of 18F-FBEM-Cys40-exendin-4 at different time points after reperfusion. The localization of 18F-FBEM-Cys40-exendin-4 accumulation was determined by coregistering 18F-FDG PET and CT images. Ex vivo autoradiography, GLP-1R immunohistochemical staining, and Western blot analysis were performed to confirm the PET results. Results: Myocardial origin and infarcted/ischemic area localization of 18F-FBEM-Cys40-exendin-4 accumulation was confirmed by coregistration of small-animal CT and 18F-FDG images. At 8 h after MI/R, tracer uptake in the infarcted/ischemic region was 0.37 ± 0.05 percentage injected dose per gram, significantly higher than that in the control group (P < 0.01). The localized tracer uptake decreased, relative to the 8-h time point, but was still significantly higher than the control group on days 1 and 3 after MI/R. At 2 wk after MI/R, the tracer uptake in the affected area showed no significant difference, compared with that in the healthy myocardium. Autoradiography showed the same trend of 18F-FBEM-Cys40-exendin-4 uptake in the myocardial infarcted/ischemic area. The specificity of tracer uptake into ischemic myocardium was supported by decreased tracer uptake after the rats were pretreated with an excess amount of unlabeled exendin-4. Immunohistochemical staining and Western blotting of GLP-1R protein of excised cardiac sections confirmed that the change in uptake observed by PET corresponded to a change in GLP-1R expression. Conclusion: Noninvasive PET using 18F-FBEM-Cys40-exendin-4 revealed a dynamic pattern of GLP-1R upregulation in the infarcted/ischemic area after MI/R. The imaging results will deepen our understanding of the mechanism of the cardioprotective effect of GLP-1 and its analogs and potentially provide guidance for optimization of the time frame of therapeutic intervention. ER -