Abstract 17146: Molecular Imaging of Chemokine Receptor Type 4 Following Myocardial Infarction
Chemokine receptor type 4 (CXCR4) is involved in the process of post-infarct inflammation and has emerged as a therapeutic target to support myocardial recovery. We aimed to non-invasively track regional tissue CXCR4 expression after myocardial infarction (MI) using the novel specific radioligand 68Ga-pentixafor (PTX) and positron emission tomography (PET). C57Bl/6 mice underwent coronary artery ligation (n=24) or no surgery (n=7). Serial PET images were acquired using PTX (10MBq) at 3d and 7d post-MI. The infarct territory was localized by a subsequent 18F-deoxyglucose scan. Fusion PET images revealed increased PTX uptake in the infarct region at 3d compared to remote myocardium (% injected dose per gram (%ID/g); 0.9±0.1 vs 0.4±0.1, p<0.01). This increase partially receded by 7d (0.7±0.1, p<0.05 to 3d). Activity in the remote myocardium was lower than in the infarct territory, as confirmed by autoradiography and sequential histopathology. FACS analysis showed infiltration of CD45-positive leukocytes in the left ventricle proportional to PTX uptake (x106, ctl 0.2±0.1; d3 1.6±0.6; d7 0.5±0.2; p=0.04). Modulation of the imaging signal was possible by co-injection of the CXCR4 inhibitor AMD3100 (50μg), which lowered the infarct signal by 21% at 3d post-MI (p<0.05). Similarly, oral administration of enalapril, which is known to lower leukocyte trafficking to the infarct, evoked a significant reduction of infarct/remote PTX uptake by 18% at d3. A parallel modest reduction of CD45-positive cells (-22% at d3, -50% at d7, p=0.02) was observed on FACS analysis. In summary, 68Ga-PTX provides a non-invasive measurement of CXCR4 expression in the damaged region post-MI, and may provide a novel method to evaluate targeted therapy to modulate inflammation and infarct repair.
Author Disclosures: J.T. Thackeray: None. Y. Wang: None. T. Derlin: None. A. Wittneben: None. J.P. Bankstahl: None. T.L. Ross: None. H. Wester: None. K.C. Wollert: None. F.M. Bengel: None.
- © 2015 by American Heart Association, Inc.