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

AimTo 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.MethodsThe 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.ResultsThe 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.ConclusionA possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.