Lectin conjugates as biospecific contrast agents for MRI. Coupling of Lycopersicon esculentum agglutinin to linear water-soluble DTPA-loaded oligomers.
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 (1)H 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.
Pashkunova-Martic
Irena
I
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, 1090, Vienna, Austria.
Kremser
Christian
C
Department of Radiology, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria.
Galanski
M S
MS
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, 1090, Vienna, Austria.
Schluga
Petra
P
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, 1090, Vienna, Austria.
Arion
Vladimir
V
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, 1090, Vienna, Austria.
Debbage
Paul
P
Department of Anatomy, Histology and Embryology, Innsbruck Medical University, Muellerstr. 59, 6020, Innsbruck, Austria.
Jaschke
Werner
W
Department of Radiology, Innsbruck Medical University, Anichstr. 35, 6020, Innsbruck, Austria.
Keppler
Bernhard
B
Institute of Inorganic Chemistry, University of Vienna, Waehringerstr. 42, 1090, Vienna, Austria. bernhard.keppler@univie.ac.at.
D000818:Animals; D002417:Cattle; D002850:Chromatography, Gel; D003287:Contrast Media; D018551:Solanum lycopersicum / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D013058:Mass Spectrometry; D004369:Pentetic Acid / Q000737:chemistry*; D037121:Plant Lectins / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D012995:Solubility; D014867:Water / Q000737:chemistry
D003287:Contrast Media; D037121:Plant Lectins; D014867:Water; D012710:Serum Albumin, Bovine; D004369:Pentetic Acid