Non-invasive assessment of activated renal macrophages by imaging of colony-stimulating factor 1 receptor in mouse model with ischemic acute kidney injury.

BACKGROUND: Emerging evidence suggests that renal inflammation, characterized by the activation of renal macrophages, plays a critical role in the pathogenesis of kidney diseases, including acute kidney injury (AKI). However, reliable research methods for visualizing renal macrophages remain limited. In this study, we utilized positron emission tomography (PET) imaging combined with a radiolabeled ligand targeting colony-stimulating factor 1 receptor (CSF1R) to assess the potential of CSF1R-PET as a non-invasive tool for examining renal inflammation. METHODS: Single-cell RNA sequencing analysis was performed to identify imaging biomarkers for activated macrophages in an ischemia-reperfusion (I/R)-induced AKI (I/R-AKI) model. We employed PET and in-vitro autoradiography with (11)C-CPPC, a CSF1R-specific radioligand, in mouse models of I/R-AKI and renal/perinephric abscesses (RA). Immunohistochemical analysis was performed to assess renal pathologies, macrophage activation, and CSF1R expression. RESULTS: Single-cell RNA sequencing analysis of publicly available data revealed a dramatic upregulation of CSF1R, primarily expressed in M2 macrophages, in response to I/R-AKI. PET and in-vitro autoradiography showed that retention of (11)C-CPPC was markedly increased in ischemic renal regions and RA-affected areas compared to normal kidney regions. Immunohistochemical analysis confirmed substantial increases in CSF1R expression and the accumulation of activated macrophages in the medullary region of I/R-AKI mice and RA-affected renal regions, supporting the in-vivo and in-vitro imaging results. CONCLUSION: Our findings provide the first evidence supporting the utility of (11)C-CPPC-PET as a clinically-available tool for non-invasive detection of activated renal macrophages, predominantly of the M2 phenotype.