title: Targeting and in vivo imaging of non-small-cell lung cancer using nebulized multimodal contrast agents.
abstract: One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this work, we evaluated the potential of optimized lung MRI techniques and nebulized ultrasmall multimodal gadolinium-based contrast agents [ultrasmall rigid platforms (USRPs)] as a completely noninvasive approach for non-small-cell lung cancer (NSCLC) in vivo detection. A mouse model of NSCLC expressing the luciferase gene was developed. Ultrashort echo-time free-breathing MRI acquisitions were performed before and after i.v. or intrapulmonary administration of the nanoparticles to identify and segment the tumor. After orotracheal or i.v. administration of USRPs, an excellent colocalization of the position the tumor with MRI, bioluminescence and fluorescence reflectance imaging, and histology was observed in all mice. Significantly higher signal enhancements and contrast-to-noise ratios were observed with orotracheal administration using lower doses, reducing the toxicity issues and the interobserver variability in tumor detection. The observations suggested the existence of an unknown original mechanism (different from the enhanced permeability and retention effect) responsible for this phenomenon. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify, and longitudinally monitor the development of submillimetric NSCLCs. The absence of ionizing radiation and high resolution MRI, along with the complete noninvasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge this is the first time that the advantages of an orotracheal administration route are demonstrated for the investigation of the pathomorphological changes due to NSCLCs.
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5536, Université Bordeaux Segalen, 33076 Bordeaux, France;
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Nano-H SAS, 38070 Saint Quentin-Fallavier, France;Institut National de la Santé et de la Recherche Médicale Unité 823 andUniversité Joseph Fourier, Institut Albert Bonniot, 38706 Grenoble, France; and.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.affiliation: Institut Lumière Matière, Unité Mixte de Recherche 5306, Université Lyon 1, Centre National de la Recherche Scientifique, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5536, Université Bordeaux Segalen, 33076 Bordeaux, France;
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Fortin
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5536, Université Bordeaux Segalen, 33076 Bordeaux, France;
authors.forename: Nawal
authors.initials: N
authors.lastname: Tassali
authors.affiliation: Institut Lumière Matière, Unité Mixte de Recherche 5306, Université Lyon 1, Centre National de la Recherche Scientifique, Université de Lyon, 69622 Villeurbanne Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Institut National de la Santé et de la Recherche Médicale Unité 823 andUniversité Joseph Fourier, Institut Albert Bonniot, 38706 Grenoble, France; and.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5536, Université Bordeaux Segalen, 33076 Bordeaux, France; yannick.cremillieux@u-bordeaux2.fr.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Crémillieux
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000000981:diagnostic imaging*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology*; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009330:Nebulizers and Vaporizers; D009368:Neoplasm Transplantation; D011859:Radiography
chemical_list: D003287:Contrast Media; D005682:Gadolinium
keywords: bioluminescence imaging; gadolinium-based nanoparticles; lung tumor; magnetic resonance imaging