Positron emission tomography imaging of human colon cancer xenografts in mice with [18F]fluorothymidine after TAS-102 treatment

334 Objectives TAS-102 is an orally-administered anticancer agent composed of α,α,α-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). The present study assessed [18F]fluorothymidine ([18F]FLT) uptake after TAS-102 administration in colon cancer xenograft models. Methods The HCT116, HT29, HCT8 and SW620 cells were exposed to FTD for 2 hrs, and then [3H]FLT uptake was measured 0, 2 and 24 hrs after further incubation. Static or two-hour dynamic [18F]FLT positron emission tomography (PET) was acquired in mice bearing HT29 or SW620 tumours, respectively before, 1 hr (day 1) and 8 days after administration of TAS-102 or TPI. Tumoural expression of TK1 was measured on days 8 and 15 in mice bearing SW620 tumours. Results FTD decreased the viability of all cell lines. [3H]FLT uptake increased after FTD treatment ( P Conclusions TAS-102 induces flared [18F]FLT uptake. Mechanisms may involve decreased dephosphorylation of [18F]FLT early after TAS-102 administration. Increased TK1 expression and/or nucleoside transporter may be related to the FLT flare at a later time. [18F]FLT PET might assess the pharmacodynamics of TAS-102 in cancer patients. Research Support This study was financially supported by Taiho Pharmaceuticals (Tokyo, Japan), by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (A062254), and by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2010-0025392). Taiho Pharmaceuticals was permitted to review the manuscript and suggest changes, but the final decision on content was exclusively retained by the authors. The authors had final responsibility for the decision to submit for publication.