PURPOSE: TAS-102 is an orally administered anticancer agent composed of 
α,α,α-trifluorothymidine (FTD) and thymidine phosphorylase inhibitor (TPI). This 
study assessed 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT) uptake after 
TAS-102 administration.
METHODS: The human colorectal carcinoma cell lines HCT116, HT29, HCT8 and SW620 
were exposed to FTD for 2 h, further incubated for 0, 2 and 24 h, and assayed 
for [(3)H]FLT uptake, nucleoside transport, thymidine kinase 1 (TK1) expression 
and TK1 activity. Static and 2-h dynamic [(18)F]FLT positron emission tomography 
(PET) was performed in mice bearing HT29 or SW620 tumours orally administered 
with vehicle or TAS-102.
RESULTS: FTD decreased the viability of all cell lines, whereas increased 
[(3)H]FLT uptake (P < 0.05). Increased nucleoside transport and/or TK1 
expression were observed 24 h after FTD, but not in 0-2 h. Static [(18)F]FLT PET 
in mice bearing HT29 tumours showed accumulation of [(18)F]FLT in tumours 1 h 
(day 1) after TAS-102. Two-hour dynamic PET in mice bearing SW620 tumours showed 
increased influx constant and volume of distribution of phosphorylated 
[(18)F]FLT on days 1 and 8 (P < 0.05) after TAS-102 with decreased 
dephosphorylation on day 1 (P < 0.001). Ex vivo studies showed that SW620 
tumours after TAS-102 had higher TK1 expression than those with vehicle on days 
8 and 15.
CONCLUSION: TAS-102 administration induces an increase in [(18)F]FLT uptake. 
Mechanisms may involve decreased dephosphorylation of [(18)F]FLT phosphate early 
after TAS-102 administration. Increased TK1 expression and/or nucleoside 
transporter may be related to increased [(18)F]FLT uptake at a later time. 
[(18)F]FLT PET has a potential to assess the pharmacodynamics of TAS-102 in 
cancer patients.