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

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.