title: Heterogeneous intratumoral distribution of gadolinium nanoparticles within U87 human glioblastoma xenografts unveiled by micro-PIXE imaging.
abstract: Metallic nanoparticles have great potential in cancer radiotherapy as theranostic drugs since, they serve simultaneously as contrast agents for medical imaging and as radio-therapy sensitizers. As with other anticancer drugs, intratumoral diffusion is one of the main limiting factors for therapeutic efficiency. To date, a few reports have investigated the intratumoral distribution of metallic nanoparticles. The aim of this study was to determine the quantitative distribution of gadolinium (Gd) nanoparticles after direct intratumoral injection within U87 human glioblastoma tumors grafted in mice, using micro-PIXE (Particle Induced X-ray Emission) imaging. AGuIX (Activation and Guiding of Irradiation by X-ray) 3 nm particles composed of a polysiloxane network surrounded by gadolinium chelates were used. PIXE results indicate that the direct injection of Gd nanoparticles in tumors results in their heterogeneous diffusion, probably related to variations in tumor density. All tumor regions contain Gd, but with markedly different concentrations, with a more than 250-fold difference. Also Gd can diffuse to the healthy adjacent tissue. This study highlights the usefulness of mapping the distribution of metallic nanoparticles at the intratumoral level, and proposes PIXE as an imaging modality to probe the quantitative distribution of metallic nanoparticles in tumors from experimental animal models with micrometer resolution.
authors.affiliation: CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France. Electronic address: acarmona@cenbg.in2p3.fr.
authors.forename: Asuncion
authors.initials: A
authors.lastname: Carmona
authors.affiliation: CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roudeau
authors.affiliation: CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: L'Homel
authors.affiliation: Institut Curie, Translational Research Department, Experimental Radiotherapy Platform, 15 Rue Georges Clémenceau, 91898 Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Pouzoulet
authors.affiliation: Institut Curie, Translational Research Department, Experimental Radiotherapy Platform, 15 Rue Georges Clémenceau, 91898 Orsay, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bonnet-Boissinot
authors.affiliation: CNRS, IN2P3, IMNC, UMR 8165, University of Paris 7 and 11, 5 Rue Georges Clemenceau, 91405 Orsay, France.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Prezado
authors.affiliation: CNRS, IN2P3, CENBG, UMR 5797, 19 Chemin Du Solarium, 33170 Gradignan, France; University of Bordeaux, CENBG, UMR 5797, F-33170 Gradignan, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Ortega
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000378:metabolism*; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry*; D013052:Spectrometry, X-Ray Emission / Q000379:methods*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured
chemical_list: D003287:Contrast Media; D005682:Gadolinium
keywords: Gadolinium; Nanoparticles; PIXE; Tumor