title: Targeting malignant glioma cells in vitro using platelet-derived growth factor AA-based conjugates.
abstract: Glioblastoma multiforme (GBM) is an unusually aggressive brain tumor; it is also highly heterogeneous. Poor prognosis and a median survival of less than 1 year, using conventional treatment, calls for development of new treatment strategies. Overexpression and/or amplification of platelet-derived growth factor alpha receptors (PDGF alpha Rs) in GBM might act as potential targets for a novel therapeutic approach. In this study, conjugates based on PDGFAA-ligand and dextran, of different sizes (10 and 40 kDa dextran), were prepared and investigated regarding targeting properties in vitro. Three human malignant glioma cell lines, U343MGa31L, U343MGaCl2:6, and U563MG, were used because of their previously reported differences in receptor expression and behavior. PDGFAA-based 10 kDa dextran iodine-125 radiolabeled conjugates showed the most favorable properties according to results achieved in accumulation, retention, and localization of cell-associated radioactivity. In comparison with dextran-(125)I-tyrosine delivered radioactivity, the PDGFAA-based dextran conjugates confirm the potential of receptor targeting.
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. maria.wester@liu.se
authors.forename: Maria Dahlström
authors.initials: MD
authors.lastname: Wester
authors.forename: Ake
authors.initials: A
authors.lastname: Wasteson
authors.forename: Annelie
authors.initials: A
authors.lastname: Lindström
mesh_terms: D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry; D016503:Drug Delivery Systems; D015870:Gene Expression; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007457:Iodine Radioisotopes / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000008:administration & dosage*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D014443:Tyrosine / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D003911:Dextrans; D007457:Iodine Radioisotopes; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; D014443:Tyrosine; D020796:Receptor, Platelet-Derived Growth Factor alpha