{"doi":"10.1164/rccm.202004-1132oc","title":"Chemokine Receptor 2–targeted Molecular Imaging in Pulmonary Fibrosis. A Clinical Trial","abstract":"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 accumulation and uptake of the radiotracer in mouse lungs. In lung tissues from patients with IPF, CCR2+ cells concentrated in perifibrotic regions and correlated with radiotracer localization (n = 21). Human imaging revealed little lung uptake in healthy volunteers (n = 7), whereas subjects with IPF (n = 4) exhibited intensive signals in fibrotic zones. Conclusions These findings support a role for imaging CCR2+ cells within the fibrogenic niche in IPF to provide a molecular target for personalized therapy and monitoring. Clinical trial registered with www.clinicaltrials.gov (NCT 03492762).","journal":"American Journal of Respiratory and Critical Care Medicine","year":2020,"id":53577,"datarank":2.723034496067691,"base_score":4.7535901911063645,"endowment":4.7535901911063645,"self_citation_contribution":0.7130385286659547,"citation_network_contribution":2.0099959674017365,"self_endowment_contribution":0.7130385286659547,"citer_contribution":2.0099959674017365,"corpus_percentile":null,"corpus_rank":null,"citation_count":115,"citer_count":86,"citers_with_citation_signal":68,"citers_with_endowment":68,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9612,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT03492762"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":276206,"name":"Sean P. 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