Could 99mTc-glucarate be used to evaluate tumour necrosis?

Autor: Perek, Nathalie, Sabido, Odile, Jeune, Nathalie, Prevot, Nathalie, Vergnon, Jean-Michel, Clotagatide, Anthony, Dubois, Francis
Předmět:
Zdroj: European Journal of Nuclear Medicine & Molecular Imaging; Jul2008, Vol. 35 Issue 7, p1290-1298, 9p, 1 Chart, 4 Graphs
Abstrakt: The aim of this study was to determine whether 99mTc-glucarate (99mTc-GLA) is a powerful and discriminant tumour necrosis marker. 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 99mTc-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 99mTc-GLA on each population have been studied. We also investigated the influence of necrosis on 99mTc-GLA uptake in a model of U937 xenografts in nude mice. The accumulation of 99mTc-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, 99mTc-GLA is distributed between the cytosolic/membrane and the nucleus fractions. In necrotic cells, 99mTc-GLA is mainly found in the nucleus fraction. In vivo investigations showed a higher 99mTc-GLA uptake in necrotic tumour than in apoptotic and control ones. 99mTc-GLA may be a useful agent to specifically evaluate tumour necrosis and may be helpful for the follow-up of patients with cancer. [ABSTRACT FROM AUTHOR]
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