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Article

Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model

1
Department of Medical Radiation Physics, Institution of Translational Medicine, Faculty of Medicine, Lund University, 20502 Malmö, Sweden
2
Truly Labs, Medicon Village, 223 63 Lund, Sweden
3
Department of Oncology and Pathology, Clinical Sciences, Lund University, 22184 84 Lund, Sweden
4
Lund University BioImaging Centre, Faculty of Medicine, Lund University, 221 42 Lund, Sweden
*
Author to whom correspondence should be addressed.
Shared last authorship.
TRISTAN-IMI Consortium (Translational Imaging in Drug Safety Assessment—Innovative Medicines Initiative) (#IB4SD-116106).
J. Clin. Med. 2020, 9(11), 3706; https://doi.org/10.3390/jcm9113706
Received: 25 September 2020 / Revised: 10 November 2020 / Accepted: 16 November 2020 / Published: 18 November 2020
(This article belongs to the Special Issue Novel Imaging Biomarkers in Drug Induced Interstitial Lung Diseases)
Non-invasive imaging biomarkers (IBs) are warranted to enable improved diagnostics and follow-up monitoring of interstitial lung disease (ILD) including drug-induced ILD (DIILD). Of special interest are IB, which can characterize and differentiate acute inflammation from fibrosis. The aim of the present study was to evaluate a PET-tracer specific for Collagen-I, combined with multi-echo MRI, in a rat model of DIILD. Rats were challenged intratracheally with bleomycin, and subsequently followed by MRI and PET/CT for four weeks. PET imaging demonstrated a significantly increased uptake of the collagen tracer in the lungs of challenged rats compared to controls. This was confirmed by MRI characterization of the lesions as edema or fibrotic tissue. The uptake of tracer did not show complete spatial overlap with the lesions identified by MRI. Instead, the tracer signal appeared at the borderline between lesion and healthy tissue. Histological tissue staining, fibrosis scoring, lysyl oxidase activity measurements, and gene expression markers all confirmed establishing fibrosis over time. In conclusion, the novel PET tracer for Collagen-I combined with multi-echo MRI, were successfully able to monitor fibrotic changes in bleomycin-induced lung injury. The translational approach of using non-invasive imaging techniques show potential also from a clinical perspective. View Full-Text
Keywords: lung imaging; interstitial lung disease (ILD); drug toxicity; Collagen-I; fibrosis; drug-induced interstitial lung disease (DIILD); magnetic resonance imaging (MRI); positron emission tomography (PET); animal model; bleomycin lung imaging; interstitial lung disease (ILD); drug toxicity; Collagen-I; fibrosis; drug-induced interstitial lung disease (DIILD); magnetic resonance imaging (MRI); positron emission tomography (PET); animal model; bleomycin
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MDPI and ACS Style

Mahmutovic Persson, I.; Fransén Pettersson, N.; Liu, J.; Falk Håkansson, H.; Örbom, A.; In ’t Zandt, R.; Gidlöf, R.; Sydoff, M.; von Wachenfeldt, K.; Olsson, L.E., on behalf of the TRISTAN Consortium Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model. J. Clin. Med. 2020, 9, 3706. https://doi.org/10.3390/jcm9113706

AMA Style

Mahmutovic Persson I, Fransén Pettersson N, Liu J, Falk Håkansson H, Örbom A, In ’t Zandt R, Gidlöf R, Sydoff M, von Wachenfeldt K, Olsson LE on behalf of the TRISTAN Consortium. Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model. Journal of Clinical Medicine. 2020; 9(11):3706. https://doi.org/10.3390/jcm9113706

Chicago/Turabian Style

Mahmutovic Persson, Irma, Nina Fransén Pettersson, Jian Liu, Hanna Falk Håkansson, Anders Örbom, René In ’t Zandt, Ritha Gidlöf, Marie Sydoff, Karin von Wachenfeldt, and Lars E. Olsson on behalf of the TRISTAN Consortium 2020. "Longitudinal Imaging Using PET/CT with Collagen-I PET-Tracer and MRI for Assessment of Fibrotic and Inflammatory Lesions in a Rat Lung Injury Model" Journal of Clinical Medicine 9, no. 11: 3706. https://doi.org/10.3390/jcm9113706

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