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

T. Márián, Judit Szabó-Péli, Eniko Németh, L. Trón, Elza Friedlander, Anna Szabó, L. Balkay, Gábor Veress, Z. Krasznai

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)56-63
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2007

Fingerprint

Neoplasms
Choline
Glucose
Bepridil
Thapsigargin
Confocal Microscopy
Positron-Emission Tomography
Cytosol
Flow Cytometry
Western Blotting
Cell Membrane
Antigens

Keywords

  • 3′,4′-Dichlorobenzamil hydrochloride
  • C-choline
  • FDG
  • Bepridil
  • Cancer cells
  • KB-R7943
  • Na/Ca exchange
  • PET

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells. / Márián, T.; Szabó-Péli, Judit; Németh, Eniko; Trón, L.; Friedlander, Elza; Szabó, Anna; Balkay, L.; Veress, Gábor; Krasznai, Z.

In: European Journal of Pharmaceutical Sciences, Vol. 30, No. 1, 01.2007, p. 56-63.

Research output: Contribution to journalArticle

Márián, T. ; Szabó-Péli, Judit ; Németh, Eniko ; Trón, L. ; Friedlander, Elza ; Szabó, Anna ; Balkay, L. ; Veress, Gábor ; Krasznai, Z. / Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells. In: European Journal of Pharmaceutical Sciences. 2007 ; Vol. 30, No. 1. pp. 56-63.
@article{8da1c32c01f24d7d992a26c7a4cf4436,
title = "Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells",
abstract = "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.",
keywords = "3′,4′-Dichlorobenzamil hydrochloride, C-choline, FDG, Bepridil, Cancer cells, KB-R7943, Na/Ca exchange, PET",
author = "T. M{\'a}ri{\'a}n and Judit Szab{\'o}-P{\'e}li and Eniko N{\'e}meth and L. Tr{\'o}n and Elza Friedlander and Anna Szab{\'o} and L. Balkay and G{\'a}bor Veress and Z. Krasznai",
year = "2007",
month = "1",
doi = "10.1016/j.ejps.2006.10.002",
language = "English",
volume = "30",
pages = "56--63",
journal = "European Journal of Pharmaceutical Sciences",
issn = "0928-0987",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Na+/Ca2+ exchanger inhibitors modify the accumulation of tumor-diagnostic PET tracers in cancer cells

AU - Márián, T.

AU - Szabó-Péli, Judit

AU - Németh, Eniko

AU - Trón, L.

AU - Friedlander, Elza

AU - Szabó, Anna

AU - Balkay, L.

AU - Veress, Gábor

AU - Krasznai, Z.

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

KW - 3′,4′-Dichlorobenzamil hydrochloride

KW - C-choline

KW - FDG

KW - Bepridil

KW - Cancer cells

KW - KB-R7943

KW - Na/Ca exchange

KW - PET

UR - http://www.scopus.com/inward/record.url?scp=33845400064&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33845400064&partnerID=8YFLogxK

U2 - 10.1016/j.ejps.2006.10.002

DO - 10.1016/j.ejps.2006.10.002

M3 - Article

C2 - 17125978

AN - SCOPUS:33845400064

VL - 30

SP - 56

EP - 63

JO - European Journal of Pharmaceutical Sciences

JF - European Journal of Pharmaceutical Sciences

SN - 0928-0987

IS - 1

ER -