Chemokine Receptor 2-targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial.

American Journal of Respiratory and Critical Care Medicine
Steven L BrodyYongjian Liu

Abstract

Rationale: Idiopathic pulmonary fibrosis (IPF) is a progressive inflammatory lung disease without effective molecular markers of disease activity or treatment responses. Monocyte and interstitial macrophages that express the C-C motif CCR2 (chemokine receptor 2) are active in IPF and central to fibrosis.Objectives: To phenotype patients with IPF for potential targeted therapy, we developed 64Cu-DOTA-ECL1i, a radiotracer to noninvasively track CCR2+ monocytes and macrophages using positron emission tomography (PET).Methods: CCR2+ cells were investigated in mice with bleomycin- or radiation-induced fibrosis and in human subjects with IPF. The CCR2+ cell populations were localized relative to fibrotic regions in lung tissue and characterized using immunolocalization, single-cell mass cytometry, and Ccr2 RNA in situ hybridization and then correlated with parallel quantitation of lung uptake by 64Cu-DOTA-ECL1i PET.Measurements and Main Results: Mouse models established that increased 64Cu-DOTA-ECL1i PET uptake in the lung correlates with CCR2+ cell infiltration associated with fibrosis (n = 72). As therapeutic models, the inhibition of fibrosis by IL-1β blockade (n = 19) or antifibrotic pirfenidone (n = 18) reduced CCR2+ macrophage ...Continue Reading

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Citations

Jan 9, 2021·Free Radical Biology & Medicine·Min LuoChunmeng Shi
Aug 14, 2020·American Journal of Respiratory and Critical Care Medicine·Sydney B Montesi
Mar 7, 2021·Biomedicines·Janette IkingChristoph Rischpler
Apr 18, 2021·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Gyu Seong HeoYongjian Liu

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NCT03492762

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GraphPad Prism

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