RESUMEN
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.
Asunto(s)
Neoplasias Encefálicas/patología , Medios de Contraste , Gadolinio , Glioma/patología , Espectroscopía de Resonancia Magnética/métodos , Compuestos Organometálicos , alfa-Ciclodextrinas , Animales , Volumen Sanguíneo/fisiología , Barrera Hematoencefálica/patología , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/fisiopatología , Circulación Cerebrovascular/fisiología , Glioma/irrigación sanguínea , Glioma/fisiopatología , Imagen por Resonancia Magnética , Ratones , Ratones Endogámicos , Modelos Cardiovasculares , Compuestos Organometálicos/síntesis química , alfa-Ciclodextrinas/síntesis químicaRESUMEN
The aim of the study was to establish a correlation between the chemical structure of amphiphilic beta-cyclodextrins (beta-CDa) and their ability to form stable nanospheres. Amphiphilic derivatives were obtained according to an optimized well-known three-step synthesis. The selective acylation of the secondary face of beta-CD being well controlled, several beta-CDa presenting different substitution degree were synthesized. The self-organization properties of the derivatives were evaluated. The peracylated beta-CD, i.e. bearing 14 alkyl chains on the secondary hydroxyl groups, does not yield stable nanosphere suspension, even in the presence of a non ionic surfactant in the aqueous phase. However, the presence of partially acylated derivatives within the beta-CDa allows self-assembly into stable nanosphere suspension.