Molecular imaging of αvβ3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA†
| Autor: | Oltea Murariu, Sophie Laurent, Carmen Burtea, David Vansthertem, A. Verbruggen, Dirk Rattat, Gérard Toubeau, Robert N. Muller, Luce Vander Elst |
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| Rok vydání: | 2008 |
| Předmět: |
Pathology
medicine.medical_specialty Physiology Angiogenesis Integrin Contrast Media Inflammation Binding Competitive Jurkat cells Jurkat Cells Mice Apolipoproteins E In vivo Physiology (medical) medicine.artery Organometallic Compounds medicine Animals Humans Rats Wistar Aorta Mice Knockout biology business.industry Signal Processing Computer-Assisted Pentetic Acid Atherosclerosis Integrin alphaVbeta3 medicine.disease Immunohistochemistry Rats Mice Inbred C57BL Disease Models Animal Atheroma Circulatory system cardiovascular system biology.protein Technetium Tc 99m Pentetate Female Radiopharmaceuticals medicine.symptom Cardiology and Cardiovascular Medicine business Magnetic Resonance Angiography |
| Zdroj: | Cardiovascular Research. 78:148-157 |
| ISSN: | 1755-3245 0008-6363 |
| DOI: | 10.1093/cvr/cvm115 |
| Popis: | The integrin alpha v beta3 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 non-invasive molecular magnetic resonance imaging (MRI) of plaque-associated alpha v beta3 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 99mTc-DTPA with alpha v beta3 integrin was furthermore confirmed on Jurkat T lymphocytes.The mimRGD was synthesized and conjugated to DTPA. DTPA-g-mimRGD was complexed with GdCl3.6H2O, EuCl3.6H2O, or with [99mTc(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 beta3 integrin were confirmed in aorta specimens by immunohistochemistry. Gd-DTPA-g-mimRGD produced a strong enhancement of the external structures of the aortic wall 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.The new compound is potentially useful for the diagnosis of vulnerable atherosclerotic plaques and of other pathologies characterized by alpha v beta3 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. |
| Databáze: | OpenAIRE |
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