Surface modification of PLGA nanospheres with Gd-DTPA and Gd-DOTA for high-relaxivity MRI contrast agents

G. Ratzinger, P. Agrawal, W. Koerner, J. Lonkai, H.M.H.F. Sanders, E. Terreno, M. Wirth, G. J. Strijkers, K. Nicolay, F. Gabor

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The preparation of particulate contrast agents for magnetic resonance imaging (MRI) based on biodegradable poly(d,l-lactide-co-glycolide) (PLGA) nanocarriers is reported. By spacer-aided covalent surface-grafting of the prominent chelating ligands diethylenetriaminepentaacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), respectively, up to 236 μg gadolinium per mg PLGA can be immobilized in a stable manner. Due to the localisation at the particle surface, water protons may effectively interact with the gadolinium chelates and the modified particles exhibit high proton relaxivities as confirmed by T1 relaxivities of up to 17.5 mm−1s−1 (25 °C, 1.41 T) in case of Gd-DOTA-functionalized carriers and also supported by NMRD profiles. The obtained values compare favorably with marketed low-molecular weight contrast agents and thus suggest suitability for in vivo use.
Originele taal-2Engels
Pagina's (van-tot)8716-8723
Aantal pagina's8
Nummer van het tijdschrift33
StatusGepubliceerd - nov 2010

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