Evaluation of imatinib mesylate effects on glioblastoma aggressiveness with SPECT radiotracer 99mTc-(v)-DMSA.
In vitro and in vivo studies have demonstrated inhibition of glioblastoma growth by imatinib mesylate (Gleevec). Imatinib is an inhibitor of the tyrosine kinase activities of platelet-derived growth factor receptor (PDGF-r), which is involved in glioblastoma aggressiveness. In this study, we have investigated the link between 99mTc-(V)-DMSA, an imaging agent used in Single Photon Emission Computed Tomography, cellular accumulation and the biological effects of imatinib mediated by PDGF-r in a human glioblastoma cell line U87-MG. Cells treated with imatinib showed significant decreases in proliferation, invasion, migration and PDGF-rbeta expression. 99mTc-(V)-DMSA cellular uptake studies showed that the specific action of imatinib on PDGF-r signal pathway, in the human glioblastoma cell line U87-MG, could be followed by radioactive tracer. Furthermore, strong correlations between cellular 99mTc-(V)-DMSA uptake and the effect of imatinib therapy on U87-MG proliferation (r=0.896), invasion (r=0.621) and migration (r=0.822) were obtained, likewise for 99mTc-(V)-DMSA uptake and PDGF-r expression (r=0.958). Our results show that the biological effects of imatinib therapy on tumour cells properties are linked to PDGF-r phosphorylation and could be traced with 99mTc-(V)-DMSA, which also seems to be a potential tracer to evaluate the response to imatinib therapy in glioblastoma.
Le Jeune
Nathalie
N
Department of Biophysics and Radiopharmaceuticals, Research group EA 3063 "Cellular Survival and Adhesion in tumours and grafts", Faculty of Medicine Jacques Lisfranc, University of Saint-Etienne, France. nathalie.lejuene@univ-st-etienne.fr
Dubois
Francis
F
Bin
Valérie
V
Perek
Nathalie
N
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D000068877:Imatinib Mesylate; D010879:Piperazines / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D000068877:Imatinib Mesylate; D017479:Receptors, Platelet-Derived Growth Factor