title: Integrin-Targeted Hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography for Imaging Tumor Progression and Early Response in Non-Small Cell Lung Cancer.
abstract: Integrins play an important role in tumor progression, invasion and metastasis. Therefore we aimed to evaluate a preclinical imaging approach applying ανβ3 integrin targeted hybrid Fluorescence Molecular Tomography/X-ray Computed Tomography (FMT-XCT) for monitoring tumor progression as well as early therapy response in a syngeneic murine Non-Small Cell Lung Cancer (NSCLC) model. Lewis Lung Carcinomas were grown orthotopically in C57BL/6 J mice and imaged in-vivo using a ανβ3 targeted near-infrared fluorescence (NIRF) probe. ανβ3-targeted FMT-XCT was able to track tumor progression. Cilengitide was able to substantially block the binding of the NIRF probe and suppress the imaging signal. Additionally mice were treated with an established chemotherapy regimen of Cisplatin and Bevacizumab or with a novel MEK inhibitor (Refametinib) for 2 weeks. While μCT revealed only a moderate slowdown of tumor growth, ανβ3 dependent signal decreased significantly compared to non-treated mice already at one week post treatment. ανβ3 targeted imaging might therefore become a promising tool for assessment of early therapy response in the future.
authors.affiliation: Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Valerie
authors.initials: V
authors.lastname: Phi Van
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Kimm
authors.affiliation: Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prakash
authors.affiliation: Chemistry Department and TUM Institute for Advanced Study, Lichtenbergstrasse 2a, D-85748, Garching, Germany.
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kosanke
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Aichler
authors.affiliation: Department of Internal Medicine II, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Aayush
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Rummeny
authors.affiliation: Department of Clinical Radiology, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany.
authors.forename: Michel
authors.initials: M
authors.lastname: Eisenblätter
authors.affiliation: Department of Internal Medicine II, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, D-69120, Heidelberg, Germany; Division of Solid Tumor Translational Oncology, German Cancer Consortium (DKTK), partner site Essen, University Hospital Essen, Hufelandstraße 55, D-45147 Essen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Siveke
authors.affiliation: Research Unit Analytical Pathology, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Axel K
authors.initials: AK
authors.lastname: Walch
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany.
authors.forename: Rickmer
authors.initials: R
authors.lastname: Braren
authors.affiliation: Institute for Biological and Medical Imaging, Helmholtz Zentrum München, Ingolstädter Landstrasse 1, D-85764 Oberschleissheim, Germany.
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.affiliation: Department of Radiology, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675, München, Germany; Department of Clinical Radiology, Universitätsklinikum Münster, Albert-Schweitzer-Campus 1, D-48149, Münster, Germany. Electronic address: moritz.wildgruber@ukmuenster.de.
authors.forename: Moritz
authors.initials: M
authors.lastname: Wildgruber
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D018450:Disease Progression; D005453:Fluorescence; D015870:Gene Expression; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000235:genetics / Q000378:metabolism; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D057054:Molecular Imaging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D014054:Tomography; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D039302:Integrin alphaVbeta3; D016023:Integrins; D047428:Protein Kinase Inhibitors