PURPOSE: Choline derivatives labelled with positron emitters are successfully used for PET imaging of prostate cancer patients. Since little is known about uptake mechanisms, the aim of this study was to characterize choline uptake in prostate cancer cells, also following anti-androgen treatment or chemotherapy.METHODS: Choline uptake in prostate cancer cells (LNCaP, PC-3) and Michaelis-Menten kinetics were analysed using different concentrations of (3)H-choline via liquid scintillation counting. Inhibition of (3)H-choline uptake was assayed in the presence of hemicholinium-3 (HC-3), unlabelled choline, guanidine and tetraethylammonium (TEA), an inhibitor of the organic cation transporter (OCT). Changes in choline uptake triggered by bicalutamide and docetaxel were evaluated and choline transporters were detected via Western blotting.RESULTS: Michaelis-Menten kinetics yielded a saturable transport with K(m) values of 6.9 and 7.0 micromol/l choline for LNCaP and PC-3 cells, respectively. Treatment of cells with bicalutamide and docetaxel caused an increase in total choline uptake but had no significant effect on K(m) values. Uptake of (3)H-choline was NaCl dependent and 4.5-fold higher in LNCaP cells than in PC-3 cells. (3)H-Choline uptake was reduced by 92-96% using HC-3 and unlabelled choline, by 63-69% using guanidine and by 20% using TEA. The high-affinity choline transporter was detected via Western blotting.CONCLUSION: Choline uptake in prostate cancer cells is accomplished both by a transporter-mediated and a diffusion-like component. Results of inhibition experiments suggest that uptake is mediated by a selective choline transporter rather than by the OCT. Bicalutamide- and docetaxel-induced changes in total choline uptake could affect PET tumour imaging.
Androgen Antagonists Anilides