NDLI: Late treatment with imatinib mesylate ameliorates radiation-induced lung fibrosis in a mouse model

Content Provider	Springer Nature : BioMed Central
Author	Li, Minglun Abdollahi, Amir Gröne, Hermann-Josef Lipson, Kenneth E Belka, Claus Huber, Peter E
Abstract	Background We have previously shown that small molecule PDGF receptor tyrosine kinase inhibitors (RTKI) can drastically attenuate radiation-induced pulmonary fibrosis if the drug administration starts at the time of radiation during acute inflammation with present but limited effects against acute inflammation. To rule out interactions of the drug with acute inflammation, we investigated here in an interventive trial if a later drug administration start at a time when the acute inflammation has subsided - has also beneficial antifibrotic effects. Methods Whole thoraces of C57BL/6 mice were irradiated with 20 Gy and treated with the RTKI imatinib starting either 3 days after radiation (during acute inflammation) or two weeks after radiation (after the acute inflammation has subsided as demonstrated by leucocyte count). Lungs were monitored and analyzed by clinical, histological and in vivo non-invasive computed tomography as a quantitative measure for lung density and lung fibrosis. Results Irradiation induced severe lung fibrosis resulting in markedly reduced mouse survival vs. non-irradiated controls. Both early start of imatinib treatment during inflammation and late imatinib start markedly attenuated the development of pulmonary fibrosis as demonstrated by clinical, histological and qualitative and quantitative computed tomography results such as reduced lung density. Both administration schedules resulted in prolonged lifespans. The earlier drug treatment start resulted in slightly stronger beneficial antifibrotic effects along all measured endpoints than the later start. Conclusions Our findings show that imatinib, even when administered after the acute inflammation has subsided, attenuates radiation-induced lung fibrosis in mice. Our data also indicate that the fibrotic fate is not only determined by the early inflammatory events but rather a complex process in which secondary events at later time points are important. Because of the clinical availability of imatinib or similar compounds, a meaningful attenuation of radiation-induced lung fibrosis in patients seems possible.
Related Links	https://ro-journal.biomedcentral.com/counter/pdf/10.1186/1748-717X-4-66.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/1748-717X-4-66
Journal	Radiation Oncology
Issue Number	1
Volume Number	4
Language	English
Publisher	BioMed Central
Publisher Date	2009-12-21
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Radiotherapy Imaging Radiology Imatinib Idiopathic Pulmonary Fibrosis Acute Inflammation Lung Fibrosis Imatinib Treatment
Content Type	Text
Resource Type	Article
Subject	Radiology, Nuclear Medicine and Imaging Oncology
Journal Impact Factor	3.3/2023
5-Year Journal Impact Factor	3.6/2023

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