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2008-01-01 - Article/Dans un journal avec peer-review - Anglais - 10 page(s)

Burtea Carmen , Laurent Sophie , Murariu Oltea , Rattat D., Toubeau Gérard, Verbruggen A., Vansthertem David, Vander Elst Luce , Muller Robert , "Molecular imaging of alpha(v)beta(3) integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA" in Cardiovascular Research, 78, 1, 148-157

  • Edition : Elsevier Science, Amsterdam (The Netherlands)
  • Codes CREF : Histologie (DI3212), Résonance magnétique nucléaire (biophysique) (DI131B), Sciences biomédicales (DI3200), Cardiologie et circulation (DI3321), Pharmacocinétique (DI3431), Chimie organique (DI1313), Imagerie médicale, radiologie, tomographie (DI3243)
  • Unités de recherche UMONS : Chimie générale, organique et biomédicale (M108), Histologie (M118)
Texte intégral :

Abstract(s) :

(Anglais) Aims The integrin alpha(v)beta(3) is highly expressed in atherosclerotic plaques by medial. and intimal smooth muscle cells and by endothelial cells of angiogenic microvessels. In this study, we have assessed noninvasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha(v)beta(3) integrin expression on transgenic ApoE(-/-) mice with a low molecular weight peptidomimetic of Arg-Gly-Asp (mimRGD) grafted to gadolinium diethylenetriaminepentaacetate (Gd-DTPA-g-mimRGD). The analogous compound Eu-DTPA-g-mimRGD was employed for an in vivo competition experiment and to confirm the molecular targeting. The specific interaction of mimRGD conjugated to Gd-DTPA or to (99)mTc-DTPA with alpha(v)beta(3) integrin was furthermore confirmed on Jurkat T lymphocytes. Methods and results The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3 center dot 6H(2)O, EuCl3 center dot 6H(2)O, or with [(99)mTc(CO)(3)(H2O)(3)](+). MRI evaluation was performed on a 4.7 T Bruker imaging system. Blood pharmacokinetics of Gd-DTPA-g-mimRGD were assessed in Wistar rats and in c57bl/6j mice. The presence of angiogenic blood vessels and the expression of alpha(v)beta(3) integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic watt and of the more profound layers (possibly tunica media and intima). The aortic lumen seemed to be restrained and distorted. Pre-injection of Eu-DTPA-g-mimRGD diminished the Gd-DTPA-g-mimRGD binding to atherosclerotic plaque and confirmed the specific molecular targeting. A slower blood clearance was observed for Gd-DTPA-g-mimRGD, as indicated by a prolonged elimination half-life and a diminished total clearance. Conclusion The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha(v)beta(3) integrin expression, such as cancer and inflammation. The delayed blood clearance, the significant enhancement of the signal-to-noise ratio, and the low immunogenicity of the mimetic molecule highlight its potential for an industrial and clinical implementation.

Identifiants :
  • DOI : 10.1093/cvr/cvm115
  • PMID : 1817429

Mots-clés :
  • (Anglais) atherosclerosis
  • (Anglais) inflammation
  • (Anglais) alpha-v beta-3
  • (Anglais) MRI contrast agents
  • (Anglais) molecular imaging
  • (Anglais) magnetic resonance imaging