title: Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells.
abstract: 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.
authors.affiliation: Positron Emission Tomograph Center, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary. marian@pet.dote.hu
authors.forename: Teréz
authors.initials: T
authors.lastname: Márián
authors.forename: Judit
authors.initials: J
authors.lastname: Szabó-Péli
authors.forename: Eniko
authors.initials: E
authors.lastname: Németh
authors.forename: Lajos
authors.initials: L
authors.lastname: Trón
authors.forename: Elza
authors.initials: E
authors.lastname: Friedlander
authors.forename: Anna
authors.initials: A
authors.lastname: Szabó
authors.forename: László
authors.initials: L
authors.lastname: Balkay
authors.forename: Gábor
authors.initials: G
authors.lastname: Veress
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Krasznai
mesh_terms: 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
chemical_list: D002250:Carbon Radioisotopes; D011849:Radioactive Tracers; D019831:Sodium-Calcium Exchanger; D019788:Fluorodeoxyglucose F18; D019284:Thapsigargin; D015764:Bepridil; D012964:Sodium; D002794:Choline; D002118:Calcium