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Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines

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Abstract

In vivo studies have demonstrated that pentavalent technetium-99m dimercaptosuccinic acid [99mTc-(V)-DMSA] may be a useful tumour imaging agent. Several studies have suggested that 99mTc-(V)-DMSA uptake may be related to the structural similarity between the 99mTc-(V)-DMSA core and the PO4 3– anion. As phosphate ions enter cells via NaPi cotransporters, we investigated whether 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporters. 99mTc-(V)-DMSA and phosphate uptake kinetics were compared in three cancer cell lines (MCF-7, G152 and MG-63) under several conditions (with and without sodium and NaPi cotransporter inhibitor and at different pH). Determination of molecular NaPi cotransporter mRNA expression was performed by reverse-transcriptase polymerase chain reaction (Rt-PCR) assay. Results obtained in the presence of NaPi inhibitor, in sodium-free medium and at alkaline pH showed that 99mTc-(V)-DMSA accumulation is linked to NaPi cotransporter functionality. MCF-7 and G152 exhibited the same tracer uptake, whereas MG-63 showed the highest phosphate accumulation and the lowest 99mTc-(V)-DMSA uptake. These results were in accordance with mRNA NaPi expression, i.e. all cell lines expressed NaPi type III but MG-63 also co-expressed NaPi type I. The total level of NaPi cotransporter was highly correlated with phosphate accumulation, while the level of type III was related to 99mTc-(V)-DMSA uptake. We have demonstrated that 99mTc-(V)-DMSA uptake is specifically mediated by NaPi type III in cancer cells.

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Acknowledgements

This work was supported by grants from the Ligue Nationale Contre le Cancer-Comité Départemental de la Loire. We thank Mr Saul for his help in the translation of the manuscript.

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  1. Laboratory of Biophysics and Radiopharmaceuticals, Cell Death and Neoplasia Group, Faculty of Medicine, University of Saint Etienne, 15 rue Ambroise Paré, 42023, Saint-Etienne cedex 02, France

    Delphine Denoyer, Nathalie Perek, Nathalie Le Jeune, Delphine Frere & Francis Dubois

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  1. Delphine Denoyer
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  2. Nathalie Perek
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  3. Nathalie Le Jeune
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  4. Delphine Frere
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Correspondence to Delphine Denoyer.

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Denoyer, D., Perek, N., Le Jeune, N. et al. Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines. Eur J Nucl Med Mol Imaging 31, 77–84 (2004). https://doi.org/10.1007/s00259-003-1334-7

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