18FDG 18FFLT 18FFAZA and 11C-Methionine Are Suitable Tracers for the Diagnosis and In Vivo Follow-Up of the Efficacy of Chemotherapy by miniPET in Both Multidrug Resistant and Sensitive Human Gynecologic Tumor Xenografts

摘要

Expression of multidrug pumps including P-glycoprotein (MDR1, ABCB1) in the plasma membrane of tumor cells often results in decreased intracellular accumulation of anticancer drugs causing serious impediment to successful chemotherapy. It has been shown earlier that combined treatment with UIC2 anti-Pgp monoclonal antibody (mAb) and cyclosporine A (CSA) is an effective way of blocking Pgp function. In the present work we investigated the suitability of four PET tumor diagnostic radiotracers including 2-[¹⁸F]fluoro-2-deoxy-D-glucose (¹⁸FDG), ¹¹C-methionine, 3′-deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT), and [¹⁸F]fluoroazomycin-arabinofuranoside (¹⁸FAZA) for in vivo follow-up of the efficacy of chemotherapy in both Pgp positive (Pgp⁺) and negative (Pgp⁻) human tumor xenograft pairs raised in CB-17 SCID mice. Pgp⁺ and Pgp⁻ A2780AD/A2780 human ovarian carcinoma and KB-V1/KB-3-1 human epidermoid adenocarcinoma tumor xenografts were used to study the effect of the treatment with an anticancer drug doxorubicin combined with UIC2 and CSA. The combined treatment resulted in a significant decrease of both the tumor size and the accumulation of the tumor diagnostic tracers in the Pgp⁺ tumors. Our results demonstrate that ¹⁸FDG, ¹⁸F-FLT, ¹⁸FAZA, and ¹¹C-methionine are suitable PET tracers for the diagnosis and in vivo follow-up of the efficacy of tumor chemotherapy in both Pgp⁺ and Pgp⁻ human tumor xenografts by miniPET.