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Ermolayev, V. ; Mohajerani, P. ; Ale, A.B.F ; Sarantopoulos, A. ; Aichler, M. ; Kayser, G.* ; Walch, A.K. ; Ntziachristos, V.

Early recognition of lung cancer by integrin targeted imaging in K-ras mouse model.

Int. J. Cancer 137, 1107-1118 (2015)
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Non-small cell lung cancer is characterized by slow progression and high heterogeneity of tumors. Integrins play an important role in lung cancer development and metastasis and were suggested as a tumor marker; however their role in anticancer therapy remains controversial. In this work, we demonstrate the potential of integrin-targeted imaging to recognize early lesions in transgenic mouse model of lung cancer based on spontaneous introduction of mutated human gene bearing K-ras mutation. We conducted ex-vivo and Fluorescence Molecular Tomography-X-ray Computed Tomography (FMT-XCT) in-vivo imaging and analysis for specific targeting of early lung lesions and tumors in rodent preclinical model for lung cancer. The lesions and tumors were characterized by histology, immunofluorescence and immunohistochemistry using a panel of cancer markers. Ex-vivo, the integrin-targeted fluorescent signal significantly differed between wild type lung tissue and K-ras pulmonary lesions at all ages studied. The panel of immunofluorescence experiments demonstrated that pulmonary lesions, which only partially show cancer cell features were detected by αvβ3-integrin targeted imaging. Human patient material analysis confirmed the specificity of target localization in different lung cancer types. Most importantly, small tumors in the lungs of 4-week-old animals could be non-invasively detected in-vivo on the fluorescence channel of FMT-XCT. Our findings demonstrated αvβ3-integrin targeted fluorescent imaging to specifically detect premalignant pleural lesions in K-ras mice. Integrin targeted imaging may find application areas in preclinical research and clinical practice, such as early lung cancer diagnostics, intraoperative assistance or therapy monitoring.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Fluorescence Molecular Tomography ; K-ras ; Non-small Cell Lung Cancer ; Preclinical Cancer Models ; X-ray Computer Tomography ; Fluorescent Contrast Agent ; Integrin; In-vivo; Molecular Tomography; Computed-tomography; Clinical-practice; Fluorescence; Angiogenesis; Expression; Invasion; Alpha(v)beta(3); Nanoparticles
Language english
Publication Year 2015
Prepublished in Year 2014
HGF-reported in Year 2014
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Journal International Journal of Cancer
Quellenangaben Volume: 137, Issue: 5, Pages: 1107-1118 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)
Research Unit Analytical Pathology (AAP)
Institute of Pathology (PATH)
POF-Topic(s) 30205 - Bioengineering and Digital Health
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505500-001
G-500390-001
G-500300-001
PubMed ID 25450481
DOI 10.1002/ijc.29372
WOS ID WOS:000356429000011
Scopus ID 84931560968
Scopus ID 84921418416
Erfassungsdatum 2014-12-04
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