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

In vitro and in vivo studies in leukaemic tumour cell line U937

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to determine whether 99mTc-glucarate (99mTc-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 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.

Results

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.

Conclusions

99mTc-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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Acknowledgements

This work was supported by grants from Ligue Nationale contre le cancer–Comite Departmental de la Loire. We thank Mr. Saul for his help in the translation of the manuscript.

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Authors and Affiliations

  1. Cancer Research Group IFRESIS 143, Faculty of Medicine, Saint-Etienne, France

    Nathalie Perek, Nathalie Le Jeune, Nathalie Prevot, Jean-Michel Vergnon, Anthony Clotagatide & Francis Dubois

  2. Flow Cytometry Center, Faculty of Medicine Jacques Lisfranc, University of Saint-Etienne, Saint-Etienne, France

    Odile Sabido

  3. Laboratoire de Biophysique, Faculté de Médecine, 15 rue Ambroise Paré, 42023, Saint-Etienne Cedex 02, France

    Nathalie Perek

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  1. Nathalie Perek
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  2. Odile Sabido
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Correspondence to Nathalie Perek.

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Perek, N., Sabido, O., Le Jeune, N. et al. Could 99mTc-glucarate be used to evaluate tumour necrosis?. Eur J Nucl Med Mol Imaging 35, 1290–1298 (2008). https://doi.org/10.1007/s00259-007-0689-6

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  • DOI: https://doi.org/10.1007/s00259-007-0689-6

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