Literature DB >> 18338166

Could 99mTc-glucarate be used to evaluate tumour necrosis? In vitro and in vivo studies in leukaemic tumour cell line U937.

Nathalie Perek1, Odile Sabido, Nathalie Le Jeune, Nathalie Prevot, Jean-Michel Vergnon, Anthony Clotagatide, Francis Dubois.   

Abstract

PURPOSE: The aim of this study was to determine whether (99m)Tc-glucarate ((99m)Tc-GLA) is a powerful and discriminant tumour necrosis marker.
MATERIALS AND METHODS: The induction of apoptosis and secondary necrosis (by a chemotherapeutic agent) and necrosis (by intense hyperthermia) was studied on an in vitro and in vivo leukaemic cell line model (U937). The percentage of apoptosis/necrosis in vitro was determined by flow cytometry after staining cells with annexin-V-fluorescein/propidium iodide. The uptake of (99m)Tc-GLA was studied after treatments that produce an optimal of necrosis cells or apoptotic cells. Three populations of interest: viable, apoptotic and necrotic cells were sorted by flow cytometry. The uptake and the intracellular distribution of (99m)Tc-GLA on each population have been studied. We also investigated the influence of necrosis on (99m)Tc-GLA uptake in a model of U937 xenografts in nude mice.
RESULTS: The accumulation of (99m)Tc-GLA in untreated and apoptotic cells was lower than in necrotic cells. Cell sorting discriminated each cellular population and showed a 14% accumulation in necrotic cells and no more than a 3% in apoptotic cells. In apoptotic and viable cells, (99m)Tc-GLA is distributed between the cytosolic/membrane and the nucleus fractions. In necrotic cells, (99m)Tc-GLA is mainly found in the nucleus fraction. In vivo investigations showed a higher (99m)Tc-GLA uptake in necrotic tumour than in apoptotic and control ones.
CONCLUSIONS: (99m)Tc-GLA may be a useful agent to specifically evaluate tumour necrosis and may be helpful for the follow-up of patients with cancer.

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Year:  2008        PMID: 18338166     DOI: 10.1007/s00259-007-0689-6

Source DB:  PubMed          Journal:  Eur J Nucl Med Mol Imaging        ISSN: 1619-7070            Impact factor:   9.236


  34 in total

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