A physiologically based pharmacokinetic model of vascular-extravascular exchanges during liver carcinogenesis: application to MRI contrast agents. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Contrast Media and Molecular Imaging Année : 2007

A physiologically based pharmacokinetic model of vascular-extravascular exchanges during liver carcinogenesis: application to MRI contrast agents.

Résumé

The extraction of physiological parameters by non-invasive imaging techniques such as dynamic magnetic resonance imaging (MRI) or positron emission tomography requires a knowledge of molecular distribution and exchange between microvascularization and extravascular tissues. These phenomena not only depend on the physicochemical characteristics of the injected molecules but also the pathophysiological state of the targeted organ. We developed a five-compartment physiologically based pharmacokinetic model focused on hepatic carcinogenesis and MRI contrast agents. This model includes physical characteristics of the contrast agent, dual specific liver supply, microvessel wall properties and transport parameters that are compatible with hepatocarcinoma development. The evolution of concentrations in the five compartments showed significant differences in the distribution of three molecules (differentiated by their diameters and diffusion coefficients ranging, respectively, from 0.9 to 62 nm and from 68.10(-9) to 47.10(-7) cm(2) s(-1)) in simulated regeneration nodules and dysplastic nodules, as well as in medium- and poorly differentiated hepatocarcinoma. These results are in agreement with known vascular modifications such as arterialization that occur during hepatocarcinogenesis. This model can be used to study the pharmacokinetics of contrast agents and consequently to extract parameters that are characteristic of the tumor development (like permeability), after fitting simulated to in vivo data.
Fichier principal
Vignette du fichier
MescamCMMI.pdf (261.27 Ko) Télécharger le fichier
Loading...

Dates et versions

inserm-00174336 , version 1 (25-09-2007)

Identifiants

Citer

Muriel Mescam, Pierre-Antoine Eliat, Claire Fauvel, Jacques D. de Certaines, Johanne Bézy-Wendling. A physiologically based pharmacokinetic model of vascular-extravascular exchanges during liver carcinogenesis: application to MRI contrast agents.. Contrast Media and Molecular Imaging, 2007, 2 (5), pp.215-28. ⟨10.1002/cmmi.147⟩. ⟨inserm-00174336⟩
128 Consultations
472 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More