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Accueil > Séminaires > Archive des séminaires d’Utinam > Archive des séminaires de chimie (jusqu’en 2011) > 2010

Novel MRI Contrast Agents for Non-Invasive Detection of Thrombosis, Inflammation and Vulnerable Plaques

par Edith Burgey -

Lundi 21 juin 2010 à 14h - Salle 18, bât N

Par Christoph Hagemeyer - Baker IDI, Melbourne

Résumé :

Molecular MRI may allow the identification of thrombosis, inflammation and vulnerable atherosclerotic plaques by detecting specific tissue markers.

It is now recognised that platelets adhering at the sites of atherosclerotic plaques contribute very early, and in an ongoing manner, to the progression of atherosclerotic disease. The thrombogenicity of atherosclerotic plaques is one of the most promising approaches to detect vulnerable plaques. The most abundantly expressed protein on the platelet surface is the integrin receptor glycoprotein GPIIb/IIIa. We previously generated small recombinant antibody fragments against ligand-induced binding sites (LIBS) on GPIIb/IIIa, which are highly specific for activated platelets.

Here we present novel targeted MRI contrast agents based on magnetic particles of iron oxide (MPIO) as well as poly-lysine gadolinium-containing dendrimers fused with single-chain antibodies against activated GPIIb/IIIa. In vitro binding studies using human thrombi confirmed the constructs target activated GPIIb/IIIa on platelets. We used these targeted particles for the detection of inflammation and thrombosis in different animal models. Immunohistochemistry of the dissected tissue confirmed specific binding to the diseased area. Our targeted imaging agents show promising results in in vivo detection of thrombosis using MR imaging.

Dr. Hagemeyer is currently a NHMRC Career Development Award Fellow (2008-2012) at Baker IDI in Melbourne. He has a background in molecular and protein biochemistry. He obtained a PhD in biochemistry from the University of Freiburg, Germany in 2001 for a thesis on steroid metabolism in the rodent brain. He changed his focus of research from neuroscience to cardiovascular science in 2002. Since then he mainly worked in the field of single-chain antibody technology, developing fusion proteins for improved and safer anticoagulation and thrombolysis as well as diagnosis of atherosclerosis.