1. ¹Institut National de la Santé et de la Recherche Médicale (INSERM), U836, La Tronche, France
2. ²Université Joseph Fourier, Grenoble Institut des Neurosciences, Grenoble, France
3. ³Laboratoire de Biophysique Cellulaire et Moléculaire CRSSA, La Tronche, France
4. ⁴Institut Fédératif de Recherche 1, CHU de Grenoble, Grenoble, France
5. ⁵Laboratoire de Reconnaissance Ionique et chimie de coordination, Service de Chimie Inorganique et Biologique (UMR-E 3 CEA-UJF), CEA/DSM/Département de Recherche Fondamentale sur la Matière Condensée, CEA-Grenoble, Grenoble, France

Correspondence: Dr H Lahrech, Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Equipe 5, Bâtiment Edmond J Safra, Chemin Fortuné Ferrini, La Tronche F-38700, France. E-mail: Hana.Lahrech@ujf-grenoble.fr

Received 4 May 2007; Revised 21 November 2007; Accepted 29 November 2007; Published online 9 January 2008.

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 T₁ method, we show the potential of gadolinium per (3,6-anhydro) -cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd³⁺ with per (3,6-anhydro)--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 T₁-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 T₁ 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.