Orotracheal administration of contrast agents: a new protocol for brain tumor targeting.
The development of new non-invasive diagnostic and therapeutic approaches is of paramount importance in order to improve the outcome of patients with glioblastoma (GBM). In this work we investigated a completely non-invasive pre-clinical protocol to effectively target and detect brain tumors through the orotracheal route, using ultra-small nanoparticles (USRPs) and MRI. A mouse model of GBM was developed. In vivo MRI acquisitions were performed before and after intravenous or orotracheal administration of the nanoparticles to identify and segment the tumor. The accumulation of the nanoparticles in neoplastic lesions was assessed ex vivo through fluorescence microscopy. Before the administration of contrast agents, MR images allowed the identification of the presence of abnormal brain tissue in 73% of animals. After orotracheal or intravenous administration of USRPs, in all the mice an excellent co-localization of the position of the tumor with MRI and histology was observed. The elimination time of the USRPs from the tumor after the orotracheal administration was approximately 70% longer compared with intravenous injection. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify and longitudinally monitor the development of GBMs. The absence of ionizing radiation and high resolution of MRI, along with the complete non-invasiveness 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 a needle-free orotracheal administration route have been demonstrated for the investigation of the pathomorphological changes due to GBMs.
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Andrea
A
Bianchi
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Damien
D
Moncelet
Institut Lumière Matière, CNRS UMR 5306, Université Claude Bernard, Domaine Scientifique de La Doua, Villeurbanne, France.
François
F
Lux
Institut Lumière Matière, CNRS UMR 5306, Université Claude Bernard, Domaine Scientifique de La Doua, Villeurbanne, France.|Nano-H SAS, Saint-Quentin Fallavier, France.
Marie
M
Plissonneau
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Silvia
S
Rizzitelli
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Emeline Julie
EJ
Ribot
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Nawal
N
Tassali
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Véronique
V
Bouchaud
Institut Lumière Matière, CNRS UMR 5306, Université Claude Bernard, Domaine Scientifique de La Doua, Villeurbanne, France.
Olivier
O
Tillement
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Pierre
P
Voisin
Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université Bordeaux Segalen, Bordeaux, France.
Yannick
Y
Crémillieux
D000284:Administration, Oral; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007089:Image Enhancement / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
MRI; contrast agents; fluorescence imaging; glioblastoma; lungs; orotracheal administration