TY - JOUR
T1 - A new macromolecular paramagnetic MR contrast agent binds to activated human platelets
AU - Chaubet, Fréderic
AU - Bertholon, Isabelle
AU - Serfaty, Jean Michel
AU - Bazeli, Ramin
AU - Alsaid, Hasan
AU - Jandrot-Perrus, Martine
AU - Zahir, Charaf
AU - Even, Pascale
AU - Bachelet, Laure
AU - Touat, Ziad
AU - Lancelot, Eric
AU - Corot, Claire
AU - Canet-Soulas, Emmanuelle
AU - Letourneur, Didier
PY - 2007/7
Y1 - 2007/7
N2 - A new functionalized macromolecular magnetic resonance (MR) contrast agent has been developed from a carboxymethyldextran-Gd(DOTA) devoid of biospecificity. The functionalized contrast agent was synthesized in order to mimic PSGL-1, the main ligand of P-selectin, a glycoprotein mainly expressed on the surface of activated platelets. The starting compound, CM1, was first carboxymethylated by monochloroacetic acid leading to a series of 10 derivatives varying in their carboxymethyl content. CM8 derivative, with a degree of substitution in carboxymethyl of 0.84, was chosen for subsequent fluorolabeling and sulfation to give CM8FS. CM8FS has an average number molecular weight of 27 000 ± 500 g/ mol, a hydrodynamic radius of 5.7 ± 0.2 nm and a high relaxivity (r1 = 11.2/mM (Gd)/s at 60 MHz). Flow cytometry experiments on whole human blood or on isolated platelets evidenced in vitro a preferential binding of CM8FS on TRAP-activated human platelets. Interestingly, CMSFS did not bind to other blood cells or to resting platelets. Pellets of TRAP-activated human platelets have also been imaged in tubes with a 1.5 T MR imager. A MR signal was observed for activated platelets incubated with CMSFS. Altogether, these in vitro results evidenced the recognition of activated human platelets by a fluorescent paramagnetic contrast agent grafted with carboxyl and sulfate groups. This biomimetic approach associated with the versatile macromolecular platform appears promising for the development of new contrast agents for molecular imaging of activated platelets in cardiovascular diseases such as atherosclerosis and aneurysms.
AB - A new functionalized macromolecular magnetic resonance (MR) contrast agent has been developed from a carboxymethyldextran-Gd(DOTA) devoid of biospecificity. The functionalized contrast agent was synthesized in order to mimic PSGL-1, the main ligand of P-selectin, a glycoprotein mainly expressed on the surface of activated platelets. The starting compound, CM1, was first carboxymethylated by monochloroacetic acid leading to a series of 10 derivatives varying in their carboxymethyl content. CM8 derivative, with a degree of substitution in carboxymethyl of 0.84, was chosen for subsequent fluorolabeling and sulfation to give CM8FS. CM8FS has an average number molecular weight of 27 000 ± 500 g/ mol, a hydrodynamic radius of 5.7 ± 0.2 nm and a high relaxivity (r1 = 11.2/mM (Gd)/s at 60 MHz). Flow cytometry experiments on whole human blood or on isolated platelets evidenced in vitro a preferential binding of CM8FS on TRAP-activated human platelets. Interestingly, CMSFS did not bind to other blood cells or to resting platelets. Pellets of TRAP-activated human platelets have also been imaged in tubes with a 1.5 T MR imager. A MR signal was observed for activated platelets incubated with CMSFS. Altogether, these in vitro results evidenced the recognition of activated human platelets by a fluorescent paramagnetic contrast agent grafted with carboxyl and sulfate groups. This biomimetic approach associated with the versatile macromolecular platform appears promising for the development of new contrast agents for molecular imaging of activated platelets in cardiovascular diseases such as atherosclerosis and aneurysms.
KW - Activated platelets
KW - Atherosclerosis
KW - Contrast agent
KW - Flow cytometry
KW - Gadolinium
KW - Magnetic resonance imaging
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U2 - 10.1002/cmmi.144
DO - 10.1002/cmmi.144
M3 - Article
C2 - 17828728
AN - SCOPUS:35148887221
SN - 1555-4309
VL - 2
SP - 178
EP - 188
JO - Contrast Media and Molecular Imaging
JF - Contrast Media and Molecular Imaging
IS - 4
ER -