{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:17:43Z","timestamp":1762157863526,"version":"3.37.3"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T00:00:00Z","timestamp":1630713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100012651","name":"Fondation Institut de Cardiologie de Montr\u00e9al","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012651","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Pulmonary hypertension (PH) complicating idiopathic pulmonary fibrosis (IPF) is associated to worse outcome. There is a great need for a non-invasive diagnostic modality to detect and evaluate the severity of pulmonary vascular disease (PVD). <jats:sup>99m<\/jats:sup>Tc-PulmoBind is a novel imaging agent that binds to the adrenomedullin (AM) receptor on the pulmonary microvascular endothelium. SPECT imaging employing the endothelial cell tracer <jats:sup>99m<\/jats:sup>Tc-PulmoBind was used to assess PVD associated with lung fibrosis.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Rats with selective right lung bleomycin-induced fibrosis were compared to control rats. SPECT imaging was performed after three weeks with <jats:sup>99m<\/jats:sup>Tc-PulmoBind and <jats:sup>99m<\/jats:sup>Tc-macroaggregates of albumin (MAA). PH and right ventricular (RV) function were assessed by echocardiography. Lung perfusion was evaluated by fluorescent microangiography. Lung AM receptor expression was measured by qPCR and by immunohistology. Relevance to human IPF was explored by measuring AM receptor expression in lung biopsies from IPF patients and healthy controls.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The bleomycin group developed preferential right lung fibrosis with remodeling and reduced perfusion as assessed with fluorescent microangiography. These rats developed PH with RV hypertrophy and dysfunction. <jats:sup>99m<\/jats:sup>Tc-PulmoBind uptake was selectively reduced by 50% in the right lung and associated with reduced AM receptor expression, PH and RV hypertrophy. AM receptor was co-expressed with the endothelial cell protein CD31 in alveolar capillaries, and markedly reduced after bleomycin. Quantitative dynamic analysis of <jats:sup>99m<\/jats:sup>Tc-PulmoBind uptake in comparison to <jats:sup>99m<\/jats:sup>Tc-MAA revealed that the latter distributed only according to flow, with about 60% increased left lung uptake while left lung uptake of <jats:sup>99m<\/jats:sup>Tc-PulmoBind was not affected. Lung from human IPF patients showed important reduction in AM receptor expression closely associated with CD31.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>SPECT imaging with <jats:sup>99m<\/jats:sup>Tc-PulmoBind detects PVD and its severity in bleomycin-induced lung fibrosis. Reduced AM receptor expression in human IPF supports further clinical development of this imaging approach.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12931-021-01836-3","type":"journal-article","created":{"date-parts":[[2021,9,4]],"date-time":"2021-09-04T18:02:27Z","timestamp":1630778547000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["SPECT imaging of pulmonary vascular disease in bleomycin-induced lung fibrosis using a vascular endothelium tracer"],"prefix":"10.1186","volume":"22","author":[{"given":"Fran\u00e7ois","family":"Harel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quang T.","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed J.","family":"Nsaibia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Finnerty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arielle","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Sirois","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louis","family":"Villeneuve","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelino","family":"Calderone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Bergeron","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emmanuelle","family":"Brochiero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Claude","family":"Tardif","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"YanFen","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3193-1014","authenticated-orcid":false,"given":"Jocelyn","family":"Dupuis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,9,4]]},"reference":[{"key":"1836_CR1","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1164\/rccm.200308-1151OC","volume":"170","author":"GP Cosgrove","year":"2004","unstructured":"Cosgrove GP, Brown KK, Schiemann WP, Serls AE, Parr JE, Geraci MW, Schwarz MI, Cool CD, Worthen GS. 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Samples of lungs explanted from patients with idiopathic pulmonary fibrosis (IPF, n\u2009=\u200911) or from lung disease-free donors (n\u2009=\u20096) were obtained from the NHLBI sponsored Lung Tissue Research Consortium and from the respiratory tissue biobank of CR-CHUM respectively. Experimental procedures received approval by the review board of each biobank and by the human ethics and research committee of the Montreal Heart Institute.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Dr. Jocelyn Dupuis is a shareholder of PulmoScience, a company that holds commercial rights to PulmoBind. All other authors have no conflict to declare.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"240"}}