Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells.

Abstract

AIM:

To establish the effects of Na(+)/Ca(2+) exchanger (NCX) blockers on 2-[(18)F]fluoro-2-deoxy-D-glucose ((18)FDG) and (11)C-choline accumulation in different cancer cells.

METHODS:

The tumor cells were incubated with NCX inhibitors, and the uptakes of (18)FDG and (11)C-choline were measured. Flow cytometric measurements of intracellular Ca(2+) and Na(+) concentrations were carried out. The presence of the NCX antigen in the cancer cells was proved by Western blotting, flow cytometry and confocal laser scanning microscopy.

RESULTS:

The NCX is expressed at a noteworthy level in the cytosol and on the cytoplasmic membrane of the examined cells. Incubation of the cells with three chemically unrelated NCX blockers (bepridil, KB-R7943 or 3',4'-dichlorobenzamil hydrochloride) resulted in an increase in the intracellular Ca(2+) concentration, with a simultaneous decrease in the intracellular Na(+) concentration. The treatment with the NCX inhibitors increased the energy consumption of the tumor cells by 50-100%. Thapsigargin abolished the NCX-induced (18)FDG accumulation in the cells. The NCX blockers applied decreased the (11)C-choline accumulation of all the investigated cancer cells by 60-80% relative to the control.

CONCLUSION:

A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.

• Authors: Teréz Márián, Judit Szabó-Péli, Eniko Németh, Lajos Trón, Elza Friedlander, Anna Szabó, László Balkay, Gábor Veress, Zoltán Krasznai
• Journal: European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences (Eur J Pharm Sci) Vol. 30 Issue 1 Pg. 56-63 (Jan 2007) ISSN: 0928-0987 [Print] Netherlands
• PMID: 17125978 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carbon Radioisotopes
• Radioactive Tracers
• Sodium-Calcium Exchanger
• Fluorodeoxyglucose F18
• Thapsigargin
• Bepridil
• Sodium
• Choline
• Calcium

Topics

• Bepridil (pharmacology)
• Calcium (metabolism)
• Carbon Radioisotopes
• Cell Line, Tumor
• Choline (pharmacokinetics)
• Flow Cytometry
• Fluorodeoxyglucose F18 (pharmacokinetics)
• Humans
• Microscopy, Confocal
• Microscopy, Fluorescence
• Neoplasms (diagnosis, metabolism)
• Positron-Emission Tomography
• Radioactive Tracers
• Sodium (metabolism)
• Sodium-Calcium Exchanger (antagonists & inhibitors, biosynthesis)
• Thapsigargin (pharmacology)