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: Hana Lahrech, Adriana-Teodora Perles-Barbacaru, Soâd Aous, Jean-François Le Bas, Jean-Claude Debouzy, Andrée Gadelle, Pascal H Fries
• Journal: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism (J Cereb Blood Flow Metab) Vol. 28 Issue 5 Pg. 1017-29 (May 2008) ISSN: 0271-678X [Print] United States
• PMID: 18183033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Contrast Media
• Organometallic Compounds
• alpha-Cyclodextrins
• gadolinium per(3,6-anhydro)-alpha-cyclodextrin
• Gadolinium
• alpha-cyclodextrin

Topics

• Animals
• Blood Volume (physiology)
• Blood-Brain Barrier (pathology)
• Brain Neoplasms (blood supply, pathology, physiopathology)
• Cerebrovascular Circulation (physiology)
• Contrast Media
• Gadolinium
• Glioma (blood supply, pathology, physiopathology)
• Magnetic Resonance Imaging
• Magnetic Resonance Spectroscopy (methods)
• Mice
• Mice, Inbred Strains
• Models, Cardiovascular
• Organometallic Compounds (chemical synthesis)
• alpha-Cyclodextrins (chemical synthesis)