Targeted PET Imaging of Chemokine Receptor 2+ Monocytes and Macrophages in the Injured Heart.

: Proinflammatory macrophages are important mediators of inflammation following myocardial infarction and allograft injury following heart transplantation. The aim of this study was to image the recruitment of proinflammatory chemokine receptor 2+ (CCR2+) cells in multiple heart injury models. Methods:64Cu-DOTA-ECL1i PET was used to image CCR2+ monocytes/macrophages in heart transplantation mouse model. Flow cytometry was performed to characterize CCR2+ cells. Autoradiography on human heart specimen was conducted to confirm binding specificity. 64Cu-/68Ga-DOTA-ECL1i were compared in ischemia/reperfusion injury mouse model. Results:64Cu-DOTA-ECL1i showed sensitive and specific detection of CCR2+ cells in all tested mouse models with comparable efficacy to 68Ga-DOTA-ECL1i. Flow cytometry demonstrated specific expression of CCR2 on monocytes/macrophages. The tracer binds to human CCR2. Conclusion: This work establishes the utility of 64Cu-DOTA-ECL1i to image CCR2+ monocytes/macrophages in mouse models and provides the requisite pre-clinical information to translate the targeted clinical grade CCR2 imaging probe for clinical investigation of heart diseases.