Clinical Imaging of Chemokine Receptor CXCR4 Early after Acute Myocardial Infarction Predicts Subsequent Ventricular Dysfunction and Remodeling

Aim: Acute myocardial infarction (MI) elicits an inflammatory response, which impacts subsequent healing. Chemokine receptor CXCR4 is highly expressed by inflammatory leukocytes and can be non-invasively measured by PET. We explored whether CXCR4 upregulation early after MI predicts left ventricular remodeling and cardiac outcome.

Methods: Cardiac MRI, perfusion SPECT, and CXCR4 PET/CT with the selective ligand ⁶⁸Ga-pentixafor were performed in 33 patients within the first week after reperfused MI. Follow-up cardiac MRI was conducted after 7.0±1.5 months. Left ventricular ejection fraction (LVEF) and area of injury (via late gadolinium enhancement) was derived from MRI. SPECT polar maps were generated and compared to normal database for calculation of infarct size. Regional standardized uptake values (SUV) were determined for CXCR4 PET, and quantitative polar maps defined the area of CXCR4 upregulation.

Results: SUV peak in the infarct territory was significantly higher than blood pool (2.4±0.5 vs. 2.0±0.3; p<0.001), but displayed high variance (1.5 to 3.8) among patients. LVEF was consistently improved at follow up (47±10 vs. 52±11%; p=0.03) and late enhancement decreased (23±8 vs. 17±6 % of LV; p<0.001). The area of CXCR4 upregulation on polar map analysis correlated with baseline LVEF (R=-0.52; p=0.004) and baseline extent of late enhancement (R=0.57; p=0.001). Notably, area of CXCR4 upregulation also correlated with follow-up LVEF (R=-0.40; p=0.022) and the change in extent of late enhancement from baseline to follow-up (R=0.36; p=0.043). Multivariate analysis identified area of CXCR4 upregulation as prognostic for LVEF, independent of infarct size.

Conclusions: These preliminary clinical data demonstrate the potential of inflammation-targeted CXCR4 PET to delineate functional outcome in patients after MI. The heterogeneity of signal among patients suggests that CXCR4 PET may facilitate candidate selection for targeted anti-inflammatory therapy.