1. Cerebral Blood Volume Quantification in a C6 Tumor Model Using Gadolinium per (3,6-Anhydro) α-Cyclodextrin as a New Magnetic Resonance Imaging Preclinical Contrast Agent
- Author
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Jean-François Le Bas, Soâd Aous, Hana Lahrech, Adriana-Teodora Perles-Barbacaru, Andrée Gadelle, Jean-Claude Debouzy, Pascal H. Fries, Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches du Service de Santé des Armées (CRSSA), Service de Santé des Armées, RMN biomédicale : de la cellule à l'homme (RBCH), Université Pierre Mendès France - Grenoble 2 (UPMF)-Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-DIR CENTRALE DU SSA-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Reconnaissance Ionique et Chimie de Coordination (RICC), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), This work was supported by the Canceropôle Lyon Auvergne Rhône-Alpes (CLARA), the EC COST Action D-38 Metal-Based Systems for Molecular Imaging Applications and the European Molecular Imaging Laboratories (EMIL) network, the Nuclear Energy Division of the Atomic Energy Commission (CEA), the GdR PARIS, the Association for the Research on Cancer (ARC) for postgraduate research grant., Collaboration, Issartel, Jean-Paul, Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: Models, Cardiovascular ,MESH: Blood Volume ,Magnetic Resonance Spectroscopy ,Gadolinium ,Contrast Media ,Blood volume ,blood–brain barrier ,MESH: Magnetic Resonance Imaging ,030218 nuclear medicine & medical imaging ,MESH: Blood-Brain Barrier ,MESH: Glioma ,Mice ,0302 clinical medicine ,MESH: Animals ,Blood Volume ,medicine.diagnostic_test ,Brain Neoplasms ,MESH: alpha-Cyclodextrins ,Models, Cardiovascular ,cerebral blood volume ,MESH: Cerebrovascular Circulation ,Glioma ,contrast agent ,Magnetic Resonance Imaging ,Extravasation ,medicine.anatomical_structure ,Neurology ,Blood-Brain Barrier ,relaxivity ,Cerebrovascular Circulation ,MESH: Brain Neoplasms ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Cardiology and Cardiovascular Medicine ,brain tumor ,alpha-Cyclodextrins ,Brain tumor ,chemistry.chemical_element ,Mice, Inbred Strains ,Blood–brain barrier ,MESH: Mice, Inbred Strains ,Nephrotoxicity ,03 medical and health sciences ,In vivo ,MESH: Contrast Media ,Organometallic Compounds ,medicine ,Animals ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,MESH: Mice ,MESH: Magnetic Resonance Spectroscopy ,business.industry ,MESH: Organometallic Compounds ,Magnetic resonance imaging ,medicine.disease ,cyclodextrin ,chemistry ,Neurology (clinical) ,MESH: Gadolinium ,Nuclear medicine ,business ,030217 neurology & neurosurgery - 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) α-cyclodextrin (Gd-ACX), a new MRI paramagnetic CA (inclusion complex of Gd3+ with per (3,6-anhydro)-α-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-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.
- Published
- 2008