Key parameters to control the design of CycloRGD multimodal Imaging contrast agent

J. Bolley, O. Haddad, E. Guenin, Y. Lalatonne, L. Motte
Paris 13 University, FR

Keywords: SPIO, RGD, avb3 targeting


Magnetic Resonance Imaging (MRI) using contrast agents is a very powerful technique for diagnostic in clinical medicine and biomedical research. The design of new magnetic nanovectors for an early detection of tumor is ambitious. The synthesis of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles targeting αvβ3 integrins and acting as new MRI contrast agents for cancer seems to be a promising way. Indeed, it is well established that αvβ3 integrin plays a key role in tumor angiogenesis acting like a receptor for the extracellular matrix proteins like vitronectin, fibronectin through the arginine-glycine-aspartic acid (RGD) sequence. Up-regulation of αvβ3 has been found to be associated with a wide range of cancers, making it a broad-spectrum tumor-market. USPIO nanocrystals are synthesized and surface passivated with bisphosphonates (BP) or catechol (CAT) derivatives bearing free reactive group (terminal COOH or alkyne function). We take advantage of the large number of these functionalities for the covalent coupling of fluorescence markers, polyethylene glycol (PEG) and cyclic RGD. Standard procedures using soluble carbodiimide (EDC) and N- hydroxysuccinimide (NHS) are used to crosslink free carboxylic acid with amino group. An other approach consists in click chemistry using an azide alkyne cycloaddition or thiol-yne chemistry.