Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by an excessive collagen deposition leading to functional decline. Therapeutic options for IPF are limited with only nintedanib and pirfenidone which are able to reduce fibrosis progression without stopping the disease. Findings new therapeutic targets and associated biomarkers are major clinical concerns. CD206-expressing M2 macrophages have been shown to be involved in fibrosis progression through secretion of pro-fibrotic cytokines, mainly TGF-β1. The kinetic and relevance of CD206⁺ macrophages recruitment during IPF remain unclear. Whether CD206⁺ macrophages may be relevant therapeutic targets or biomarkers remain an open question.

In our study, CD206⁺ lung macrophages were monitored in bleomycin-induced lung fibrosis in mice and IPF biopsies by combining flow cytometry and in vivo molecular imaging using a SPECT radiotracer, ^99mTc-Tilmnaocept, specifically targeting CD206. Fibrosis progression was monitored using a PET radiotracer, ⁶⁸Ga-collagelin, specifically binding to collagen.

We demonstrated that the pool of CD206⁺ macrophages was increased in correlation with collagen in bleomycin-induced lung fibrosis from early (D7) to advanced stages (D21) of the disease and in IPF biopsies. Interestingly, flow cytometry and ^99mTc-Tilmanocept were able to show a decrease in CD206⁺ lung macrophages upon treatment with nintedanib and tofacitinib, known as inhibitors of M2 macrophages.

M2 macrophages inhibition appears as a promising anti-fibrotic strategy and molecular imaging of CD206 may represent an innovative tool for patient selection and monitoring. CD206 may be a relevant theranostic target towards personalized medicine in IPF.