title: Evidence that 99mTc-(V)-DMSA uptake is mediated by NaPi cotransporter type III in tumour cell lines.
abstract: In vivo studies have demonstrated that pentavalent technetium-99m dimercaptosuccinic acid [(99m)Tc-(V)-DMSA] may be a useful tumour imaging agent. Several studies have suggested that (99m)Tc-(V)-DMSA uptake may be related to the structural similarity between the (99m)Tc-(V)-DMSA core and the PO(4)(3-) anion. As phosphate ions enter cells via NaPi cotransporters, we investigated whether (99m)Tc-(V)-DMSA uptake is mediated by NaPi cotransporters. (99m)Tc-(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 (99m)Tc-(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 (99m)Tc-(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 (99m)Tc-(V)-DMSA uptake. We have demonstrated that (99m)Tc-(V)-DMSA uptake is specifically mediated by NaPi type III in cancer cells.
authors.affiliation: 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@univ-st-etienne.fr
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perek
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Jeune
authors.forename: Delphine
authors.initials: D
authors.lastname: Frere
authors.forename: Francis
authors.initials: F
authors.lastname: Dubois
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D045744:Cell Line, Tumor / Q000000981:diagnostic imaging / Q000378:metabolism; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008657:Metabolic Clearance Rate; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D012516:Osteosarcoma / Q000000981:diagnostic imaging / Q000378:metabolism; D010710:Phosphates / Q000493:pharmacokinetics*; D010761:Phosphorus Radioisotopes / Q000493:pharmacokinetics; D017680:Potassium Compounds / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D012964:Sodium / Q000378:metabolism; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D027981:Symporters / Q000378:metabolism*; D019783:Technetium Tc 99m Dimercaptosuccinic Acid / Q000493:pharmacokinetics*
chemical_list: D014408:Biomarkers, Tumor; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D017680:Potassium Compounds; D019275:Radiopharmaceuticals; D050608:Sodium-Phosphate Cotransporter Proteins; D050609:Sodium-Phosphate Cotransporter Proteins, Type I; D027981:Symporters; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D012964:Sodium; C013216:potassium phosphate