Targeting malignant glioma cells in vitro using platelet-derived growth factor AA-based conjugates.
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.
Wester
Maria Dahlström
MD
Division of Cell Biology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden. maria.wester@liu.se
Wasteson
Ake
A
Lindström
Annelie
A
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
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