title: Cerebral blood volume quantification in a C6 tumor model using gadolinium per (3,6-anhydro) alpha-cyclodextrin as a new magnetic resonance imaging preclinical contrast agent.
abstract: In magnetic resonance imaging (MRI), cerebral blood volume (CBV) quantification is dependent on the MRI sequence and on the properties of the contrast agents (CAs). By using the rapid steady-state T(1) method, we show the potential of gadolinium per (3,6-anhydro) alpha-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd(3+) with per (3,6-anhydro)-alpha-cyclodextrin), for the CBV quantification in the presence of blood-brain barrier lesions. After biocompatibility and relaxivity experiments, in vivo experiments on rats were performed on a C6 tumor model with 0.05 mmol Gd-ACX/kg (<1/10 of the median lethal dose) injected at a 25 mmol/L concentration, inducing neither nephrotoxicity nor hemolysis. On T(1)-weighted images, a signal enhancement of 170% appeared in vessels after injection, but not in the tumor (during the 1 h of observation), in contrast to the 90% signal enhancement obtained with Gd-DOTA (a clinical MRI CA) injected at a T(1) isoefficient dose. This result shows the absence of Gd-ACX extravasation into the tumor tissue and its confinement to the vascular space. Fractional CBV values were found similar to Gd-ACX and Gd-DOTA in healthy brain tissue and in the contralateral hemisphere of tumor-bearing rats, whereas only Gd-ACX was appropriate for CBV quantification in tumor regions.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U836, La Tronche, France. Hana.Lahrech@ujf-grenoble.fr
authors.forename: Hana
authors.initials: H
authors.lastname: Lahrech
authors.forename: Adriana-Teodora
authors.initials: AT
authors.lastname: Perles-Barbacaru
authors.forename: Soâd
authors.initials: S
authors.lastname: Aous
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Le Bas
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Debouzy
authors.forename: Andrée
authors.initials: A
authors.lastname: Gadelle
authors.forename: Pascal H
authors.initials: PH
authors.lastname: Fries
mesh_terms: D000818:Animals; D001810:Blood Volume / Q000502:physiology; D001812:Blood-Brain Barrier / Q000473:pathology; D001932:Brain Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D003287:Contrast Media; D005682:Gadolinium; D005910:Glioma / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D051379:Mice; D008815:Mice, Inbred Strains; D008955:Models, Cardiovascular; D009942:Organometallic Compounds / Q000138:chemical synthesis; D047391:alpha-Cyclodextrins / Q000138:chemical synthesis
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; D047391:alpha-Cyclodextrins; C529671:gadolinium per(3,6-anhydro)-alpha-cyclodextrin; D005682:Gadolinium; C032613:alpha-cyclodextrin