Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells

Zoárd Tibor Krasznai, Judit Péli-Szabó, Eniko Németh, L. Balkay, Gábor Szabó, K. Goda, L. Galuska, L. Trón, Tamás Major, Z. Hernádi

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aim: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. Methods: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [99mTc]hexakis-2-methoxybutyl isonitrile (99mTc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers 11C-choline and 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. Results: The 18FDG measurements revealed that the glucose metabolic rate was significantly higher (p <0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70 μM) increased the 18FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their 11C-choline uptake. Paclitaxel reinstated the 99mTc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). Conclusion: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

Original languageEnglish
Pages (from-to)249-256
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume28
Issue number3
DOIs
Publication statusPublished - Jun 2006

Fingerprint

P-Glycoprotein
Paclitaxel
Neoplasms
Glucose
Rhodamine 123
Daunorubicin
Choline
Flow Cytometry
B-Lymphocytes
Lymphocytes

Keywords

  • C-choline
  • FDG
  • Tc-MIBI
  • MDR
  • Paclitaxel

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells. / Krasznai, Zoárd Tibor; Péli-Szabó, Judit; Németh, Eniko; Balkay, L.; Szabó, Gábor; Goda, K.; Galuska, L.; Trón, L.; Major, Tamás; Hernádi, Z.

In: European Journal of Pharmaceutical Sciences, Vol. 28, No. 3, 06.2006, p. 249-256.

Research output: Contribution to journalArticle

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abstract = "Aim: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. Methods: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [99mTc]hexakis-2-methoxybutyl isonitrile (99mTc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers 11C-choline and 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. Results: The 18FDG measurements revealed that the glucose metabolic rate was significantly higher (p <0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70 μM) increased the 18FDG uptake (up to 200{\%}) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their 11C-choline uptake. Paclitaxel reinstated the 99mTc-MIBI accumulation of the A2780AD cells (to 1500{\%} of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200{\%} of the control). Conclusion: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.",
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AU - Krasznai, Zoárd Tibor

AU - Péli-Szabó, Judit

AU - Németh, Eniko

AU - Balkay, L.

AU - Szabó, Gábor

AU - Goda, K.

AU - Galuska, L.

AU - Trón, L.

AU - Major, Tamás

AU - Hernádi, Z.

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N2 - Aim: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. Methods: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [99mTc]hexakis-2-methoxybutyl isonitrile (99mTc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers 11C-choline and 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. Results: The 18FDG measurements revealed that the glucose metabolic rate was significantly higher (p <0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70 μM) increased the 18FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their 11C-choline uptake. Paclitaxel reinstated the 99mTc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). Conclusion: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

AB - Aim: To study how paclitaxel treatment modifies the accumulation of tumor-diagnostic radiotracers in P-glycoprotein (P-gp) positive and negative cancer cells. Methods: The accumulations of different P-gp substrates, including rhodamine 123, daunorubicin and [99mTc]hexakis-2-methoxybutyl isonitrile (99mTc-MIBI), were measured in P-gp-positive (A2780AD) and P-gp-negative human ovarian carcinoma cells (A2780) and JY human lymphoid B cells. The uptakes of the tumor-diagnostic tracers 11C-choline and 2-[18F]fluoro-2-deoxy-d-glucose (18FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry. Results: The 18FDG measurements revealed that the glucose metabolic rate was significantly higher (p <0.01) in the P-gp-positive A2780AD cells than in the P-gp-negative cells. Paclitaxel (1-70 μM) increased the 18FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their 11C-choline uptake. Paclitaxel reinstated the 99mTc-MIBI accumulation of the A2780AD cells (to 1500% of the control) in a concentration-dependent manner, while it increased the uptake of the P-gp-negative cells to a lesser extent (to a maximum of 200% of the control). Conclusion: Paclitaxel modifies the uptake of tumor-diagnostic tracers in both P-gp-dependent and independent manners. Interpretation of the multifactorial effects of paclitaxel may promote a correct in vivo diagnosis of P-gp-positive and P-gp-negative tumors.

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