title: Phenylboronate 160Tb complexes for molecular recognition of glycoproteins expressed on tumor cells.
abstract: The over-expression of sialic acid on the surface of cancer cells compared with normal ones makes this nine-carbon sugar an attractive biomarker for molecular diagnosis and therapy. Here, we describe a study on the molecular recognition of sialic acid end groups on the surface of human glioma cells by (160)Tb-DTPA-EN(2), (160)Tb-DTPA-(ENPBA)(2) and (160)Tb-DTPA-(PBA)(2) complexes. The results show Tb-DTPA-(ENPBA)(2) to be the most efficient targeting agent, due to the electrostatic interaction between its two positively charged ammonium groups and the negatively charged cell surface, which provides an additional stabilization of the covalent binding through the PBA moieties and the sialic acid diol functions. Up to 5.5 nmol Tb/mg protein is taken up by the cells. ICP analysis after incubation experiments with non-radioactive Tb-DTPA-(ENPBA)(2) suggests that dissociation of Tb from this complex occurs after its binding to the cell surface. Most likely, most of the free Tb remains adsorbed on the surface of the cells, although internalization of a small amount cannot be excluded.
authors.affiliation: Biocatalysis and Organic Chemistry, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands.
authors.forename: Kristina
authors.initials: K
authors.lastname: Djanashvili
authors.forename: Gerben A
authors.initials: GA
authors.lastname: Koning
authors.forename: Astrid J G M
authors.initials: AJ
authors.lastname: van der Meer
authors.forename: Hubert Th
authors.initials: HT
authors.lastname: Wolterbeek
authors.forename: Joop A
authors.initials: JA
authors.lastname: Peters
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001897:Boronic Acids / Q000493:pharmacokinetics*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005910:Glioma / Q000000981:diagnostic imaging / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D011868:Radioisotopes / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013725:Terbium / Q000493:pharmacokinetics*
chemical_list: D014408:Biomarkers, Tumor; D001897:Boronic Acids; D006023:Glycoproteins; D009363:Neoplasm Proteins; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D013725:Terbium; D019158:N-Acetylneuraminic Acid; C010686:benzeneboronic acid