title: A new gadolinium-based contrast agent for magnetic resonance imaging of brain tumors: kinetic study on a C6 rat glioma model.
abstract: T1-weighted magnetic resonance imaging (MRI) was used to evaluate the potential interest of a new Gd-based contrast agent, termed P760, to characterize brain tumor heterogeneity and vascularization and to delineate regions containing permeable vessels. The C6 rat glioma model was used as a model of high-grade glioblastoma. The signal enhancement was measured as a function of time in the vascular compartment and in different regions of interest (ROIs) within the tumor after the injection of 0.02 mmol x kg(-1) of P760. The results were compared to those obtained after the injection of 0.1 mmol x kg(-1) of Gd-DOTA. We showed that P760, in spite of a Gd concentration five times smaller, produces an enhancement in the blood pool similar to that produced by Gd-DOTA. It was shown that P760 makes possible an excellent delineation of regions containing vessels with a damaged blood-brain barrier (BBB). Images acquired 5-10 minutes after P760 injection showed the location of permeable vessels more accurately than Gd-DOTA-enhanced images. The enhancement produced in the tumor by P760 was, however, less than that produced by Gd-DOTA. The extravasation and/or diffusion rate of P760 in the interstitial medium were found to be strongly reduced, compared to those found with Gd-DOTA. This study suggests that the new contrast agent has promising capabilities in clinical imaging of brain tumors.
authors.affiliation: Unité mixte INSERM/Université Joseph Fourier, RMN Bioclinique U 438, LRC-CEA, Hôpital Albert Michallon, Grenoble, France.
authors.forename: E
authors.initials: E
authors.lastname: Fonchy
authors.forename: H
authors.initials: H
authors.lastname: Lahrech
authors.forename: A
authors.initials: A
authors.lastname: François-Joubert
authors.forename: R
authors.initials: R
authors.lastname: Dupeyre
authors.forename: S
authors.initials: S
authors.lastname: Benderbous
authors.forename: C
authors.initials: C
authors.lastname: Corot
authors.forename: R
authors.initials: R
authors.lastname: Farion
authors.forename: C
authors.initials: C
authors.lastname: Rubin
authors.forename: M
authors.initials: M
authors.lastname: Décorps
authors.forename: C
authors.initials: C
authors.lastname: Rémy
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000175:diagnosis*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D005909:Glioblastoma / Q000175:diagnosis*; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C120577:gadolinium compound P760; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D005682:Gadolinium