Paclitaxel modifies the accumulation of tumor-diagnostic tracers in different ways in P-glycoprotein-positive and negative cancer cells.
OBJECTIVE
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 [(99m)Tc]hexakis-2-methoxybutyl isonitrile ((99m)Tc-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 (11)C-choline and 2-[(18)F]fluoro-2-deoxy-d-glucose ((18)FDG) were measured in the same cell lines. The P-gp expression and function were demonstrated by flow-cytometry.


RESULTS
The (18)FDG 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 (1-70microM) increased the (18)FDG uptake (up to 200%) of both P-gp-positive and P-gp-negative cells, whereas it did not modulate their (11)C-choline uptake. Paclitaxel reinstated the (99m)Tc-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).


CONCLUSIONS
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.
Krasznai
Zoárd Tibor
ZT
Department of Obstetrics and Gynecology, University of Debrecen, Medical and Health Science Centre, Hungary. zoardt@jaguar.dote.hu
Péli-Szabó
Judit
J
Németh
Eniko
E
Balkay
László
L
Szabó
Gábor
G
Goda
Katalin
K
Galuska
László
L
Trón
Lajos
L
Major
Tamás
T
Hernádi
Zoltán
Z
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D045744:Cell Line, Tumor / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D017239:Paclitaxel / Q000378:metabolism*; D011485:Protein Binding; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals / Q000378:metabolism*; D017256:Technetium Tc 99m Sestamibi / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; D017256:Technetium Tc 99m Sestamibi; D017239:Paclitaxel