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.
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.
Lahrech
Hana
H
Institut National de la Santé et de la Recherche Médicale, U836, La Tronche, France. Hana.Lahrech@ujf-grenoble.fr
Perles-Barbacaru
Adriana-Teodora
AT
Aous
Soâd
S
Le Bas
Jean-François
JF
Debouzy
Jean-Claude
JC
Gadelle
Andrée
A
Fries
Pascal H
PH
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
D003287:Contrast Media; D009942:Organometallic Compounds; D047391:alpha-Cyclodextrins; C529671:gadolinium per(3,6-anhydro)-alpha-cyclodextrin; D005682:Gadolinium; C032613:alpha-cyclodextrin