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


CONCLUSIONS
A possible masking effect of NCX medication must be taken into consideration during the diagnostic interpretation of PET scans.
Márián
Teréz
T
Positron Emission Tomograph Center, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. marian@pet.dote.hu
Szabó-Péli
Judit
J
Németh
Eniko
E
Trón
Lajos
L
Friedlander
Elza
E
Szabó
Anna
A
Balkay
László
L
Veress
Gábor
G
Krasznai
Zoltán
Z
D015764:Bepridil / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002250:Carbon Radioisotopes; D045744:Cell Line, Tumor; D002794:Choline / Q000493:pharmacokinetics*; D005434:Flow Cytometry; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000175:diagnosis / Q000378:metabolism; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D019284:Thapsigargin / Q000494:pharmacology
D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D019831:Sodium-Calcium Exchanger; D019788:Fluorodeoxyglucose F18; D019284:Thapsigargin; D015764:Bepridil; D012964:Sodium; D002794:Choline; D002118:Calcium