Abstract
Magnetic resonance imaging (MRI) requires synthesis of contrast media bearing targeting groups and numerous gadolinium chelating groups generating high relaxivity. This paper explores the results of linking the gadolinium chelates to the targeting group, a protein molecule, via various types of linkers. Polycondensates of diethylenetriaminepentaacetic acid (DTPA) with either diols or diamines were synthesised and coupled to the targeting group, a lectin (Lycopersicon esculentum agglutinin, tomato lectin) which binds with high affinity to specific oligosaccharide configurations in the endothelial glycocalyx. The polycondensates bear up to four carboxylic groups per constitutive unit. Gd-chelate bonds are created through dative interactions with the unshared pair of electrons on each oxygen and nitrogen atom on DTPA. This is mandatory for complexation of Gd(III) and avoidance of the severe toxicity of free gadolinium ions. The polymer–DTPA compounds were characterised by 1H NMR and mass spectrometry. The final lectin–DTPA–polycondensate conjugates were purified by fast protein liquid chromatography (FPLC). The capacity for specific binding was assessed, and the MRI properties were examined in order to evaluate the use of these oligomers as components of selective perfusional contrast agents.
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We gratefully appreciate the support of the Austrian National Bank, Jubilee project Numbers 9273 and 10844, and the excellent support of Ms. Silvia Fill, Medical University Innsbruck.
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Significance: New lectin-targeted contrast agents bearing Gd-chelates via four oligomeric linkers were prepared and characterised in order to evaluate their potential as selective contrast media for molecular imaging.
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Pashkunova-Martic, I., Kremser, C., Galanski, M.S. et al. Lectin Conjugates as Biospecific Contrast Agents for MRI. Coupling of Lycopersicon esculentum Agglutinin to Linear Water-Soluble DTPA-Loaded Oligomers. Mol Imaging Biol 13, 432–442 (2011). https://doi.org/10.1007/s11307-010-0358-1
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DOI: https://doi.org/10.1007/s11307-010-0358-1