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  • Title: Influence of Pi3-K and PKC activity on 99mTc-(V)-DMSA uptake: correlation with tumour aggressiveness in an in vitro malignant glioblastoma cell line model.
    Author: Le Jeune N, Perek N, Dubois F.
    Journal: Eur J Nucl Med Mol Imaging; 2006 Oct; 33(10):1206-13. PubMed ID: 16763818.
    Abstract:
    PURPOSE: Intensive proliferation and a high degree of migration and invasion are characteristic features of malignant glioblastomas, associated with a poor prognosis. Phosphatidylinositol-3-kinase (Pi3-K) and protein kinase C (PKC) are two phosphorylated proteins involved in glioblastoma cell progression. Phosphorylated focal adhesion protein kinase (FAK) has also been reported to be involved in tumour progression. In a recent study, we demonstrated a correlation between phosphorylated FAK, proliferation rate and 99mTc-(V)-dimercaptosuccinate [(V)-DMSA] uptake. We hypothesised that 99mTc-(V)-DMSA could be a potential imaging agent to evaluate glioblastoma aggressiveness. The aim of the present study was to assess the relationship between 99mTc-(V)-DMSA incorporation rate and modulation of Pi3-K and PKC activity. METHODS: Proliferation, migration and invasion capacities in the presence of protein kinase modulators-staurosporine (PKC inhibitor), 4-phorbol 12-myristate 13-acetate (PMA; PKC activator) and LY294002 (Pi3-K inhibitor)-were correlated with 99mTc-(V)-DMSA cell accumulation in an in vitro model of several malignant glioma cells: G111 (grade II), U-87-MG (grade III) and G152 (grade IV). RESULTS: In all cell lines tested, LY294002 and staurosporine treatment inhibited cell proliferation, migration and invasion. In contrast, treatment with PMA stimulated tumour aggressiveness. 99mTc-(V)-DMSA uptake was strongly correlated with the % of cellular proliferation (r=0.8462) and the % of cellular migration (r=0.9081), and to a lesser extent with the % of cellular invasion (r=0.7761). CONCLUSION: Our results clearly demonstrated that 99mTc-(V)-DMSA reflects Pi3-K and PKC activity and is correlated with tumour aggressiveness. 99mTc-(V)-DMSA could be a reliable in vivo marker providing additional information on the biological status of malignant glioblastoma.
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