Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease Induced by Bleomycin

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Mahmutovic Persson, IrmaLund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Medical Radiation Physics, Malmö,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments (author)

Imaging Biomarkers and Pathobiological Profiling in a Rat Model of Drug-Induced Interstitial Lung Disease Induced by Bleomycin

Article/chapterEnglish2020

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2020-06-19
Frontiers Media SA,2020

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LIBRIS-ID:oai:lup.lub.lu.se:314dc8ff-e625-462a-b71f-9a1275b1856d
https://lup.lub.lu.se/record/314dc8ff-e625-462a-b71f-9a1275b1856dURI
https://doi.org/10.3389/fphys.2020.00584DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

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A large number of systemically administered drugs have the potential to cause drug-induced interstitial lung disease (DIILD). We aim to characterize a model of DIILD in the rat and develop imaging biomarkers (IBs) for detection and quantification of DIILD. In this study, Sprague–Dawley rats received one single dose of intratracheal (i.t.) bleomycin and were longitudinally imaged at day 0, 3, 7, 14, 21, and 28 post dosing, applying the imaging techniques magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT). Bronchoalveolar lavage fluid (BALF) was analyzed for total protein and inflammatory cells. Lungs were saved for further evaluation by gene analysis using quantitative-PCR and by histology. Lung sections were stained with Masson’s-Trichrome staining and evaluated by modified Ashcroft score. Gene expression profiling of inflammatory and fibrotic markers was performed on lung tissue homogenates. Bleomycin induced significant increase in total protein concentration and total cell count in bronchoalveolar lavage (BAL), peaking at day 3 (p > 0.001) and day 7 (p > 0.001) compared to control, respectively. Lesions measured by MRI and PET signal in the lungs of bleomycin challenged rats were significantly increased during days 3–14, peaking at day 7. Two subgroups of animals were identified as low- and high-responders by their different change in total lung volume. Both groups showed signs of inflammation initially, while at later time points, the low-responder group recovered toward control, and the high-responder group showed sustained lung volume increase, and significant increase of lesion volume (p < 0.001) compared to control. Lastly, important inflammatory and pro-fibrotic markers were assessed from lung tissue, linking observed imaging pathological changes to gene expression patterns. In conclusion, bleomycin-induced lung injury is an adequate animal model for DIILD studies and for translational lung injury assessment by MRI and PET imaging. The scenario comprised disease responses, with different fractions of inflammation and fibrosis. Thereby, this study improved the understanding of imaging and biological biomarkers in DIILD and lung injury.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Radiologi och bildbehandling hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Radiology, Nuclear Medicine and Medical Imaging hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Lungmedicin och allergi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Respiratory Medicine and Allergy hsv//eng
animal model
bleomycin
drug-induced interstitial lung disease
imaging
inflammation
lung injury
magnetic resonance imaging
positron emission tomography

Added entries (persons, corporate bodies, meetings, titles ...)

Falk Håkansson, HannaTruly Labs (author)
Örbom, AndersLund University,Lunds universitet,Forskningsgruppen för Systemisk strålterapi,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Strålterapi,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Systemic Radiation Therapy Group,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Radiation therapy,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-aom (author)
Liu, JianTruly Labs (author)
von Wachenfeldt, KarinTruly Labs (author)
Olsson, Lars E.Lund University,Lunds universitet,Medicinsk strålningsfysik, Malmö,Forskargrupper vid Lunds universitet,Medical Radiation Physics, Malmö,Lund University Research Groups(Swepub:lu)rfa-lol (author)
Medicinsk strålningsfysik, MalmöForskargrupper vid Lunds universitet (creator_code:org_t)
TRISTAN Consortium

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