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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-10-2006 | Molecular imaging

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

Authors: Nathalie Le Jeune, Nathalie Perek, Francis Dubois

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2006

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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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
Authors: Nathalie Le Jeune
Nathalie Perek
Francis Dubois
Publication date: 01-10-2006
Publisher: Springer-Verlag
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2006
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-006-0122-6

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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

Abstract

Purpose

Methods

Results

Conclusion

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Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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