Evaluation of imatinib mesylate effects on glioblastoma aggressiveness with SPECT radiotracer 99mTc-(v)-DMSA

Abstract

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.