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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Abstract

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.
Original languageEnglish
Pages (from-to)8716-8723
Number of pages8
JournalBiomaterials
Volume31
Issue number33
DOIs
Publication statusPublished - Nov 2010

Keywords

  • Nanoparticle
  • MRI (magnetic resonance imaging)
  • Surface modification
  • Poly(D,L-lactide-co-glycolide)
  • Gadolinium
  • Chelate

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