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

Abstract

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.