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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 1/2004

01-01-2004 | Original Article

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

Authors: Delphine Denoyer, Nathalie Perek, Nathalie Le Jeune, Delphine Frere, Francis Dubois

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 1/2004

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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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Metadata
Title
Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines
Authors
Delphine Denoyer
Nathalie Perek
Nathalie Le Jeune
Delphine Frere
Francis Dubois
Publication date
01-01-2004
Publisher
Springer-Verlag
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 1/2004
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-003-1334-7

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