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

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• 关键词：Na⁺/Ca²⁺ exchange ; Cancer cells ; Bepridil ; KB-R7943 ; 3′ ; 4′ ; -Dichlorobenzamil hydrochloride ; ¹⁸FDG ; ¹¹C-choline ; PET
• 刊名：European Journal of Pharmaceutical Sciences
• 出版年：2007
• 期刊代码：15_09280987
• 类别：pha
• 出版时间：January 2007
• 卷：30
• 期：1
• 页码：56-63
• 文件大小：834 K

摘要

>Aim

To establish the effects of Na⁺/Ca²⁺ exchanger (NCX) blockers on 2-[¹⁸F]fluoro-2-deoxy-d-glucose (¹⁸FDG) and ¹¹C-choline accumulation in different cancer cells.

Methods

The tumor cells were incubated with NCX inhibitors, and the uptakes of ¹⁸FDG and ¹¹C-choline were measured. Flow cytometric measurements of intracellular Ca²⁺ 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 Ca²⁺ 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 ¹⁸FDG accumulation in the cells. The NCX blockers applied decreased the ¹¹C-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.