Alkyl-fluorinated thymidine derivatives for imaging cell proliferation -: II.: Synthesis and evaluation of N3-(2-[18F]fluoroethyl)-thymidine

We prepared N-3-(2-[F-18]fluoroethyl)-thymidine ([F-18]NFT202) and examined its potential as a positron emission tomography (PET) ligand for imaging cellular proliferation. [F-18]NFT202 was synthesized from 3',5'-di-O-toluoyl-N-3-(2-p-toluenesulfoxyethyl)-thymidine in a two-step reaction. N-3-(2-fluoroethyl)-[2-C-14]thymidine ([C-14]NFT202) was also synthesized from [2- C-14]thymidine in a one-step reaction. Whereas [F-18]NFT202 did not accumulate in mouse Lewis lung carcinoma tumors, 3-[18F]3-fluoro-3'-deoxytbymidine ([F-18]FLT) showed significantly high uptake. To clarify this unexpected result, we evaluated the cell uptake of [C-14]NFT202 in vitro. The uptake was approximately eight times higher in thymidine kinase 1 (TK1)+ clones (L-M cells) than in TK1-deficient mutant L-M(TK-) cells (P <.01, Student's t test). In addition, we observed a positive correlation between tracer uptake and the S-phase fraction. However, the net in vitro tumor cell uptake of [C-14]NFT202 was lower than that of [2-C-14]3'-fluoro-3'-deoxythymidine. [C-14]NFT202 was not effectively incorporated into the DNA fraction and was indeed washed out from tumor cells. These results clearly showed that [F-18]NFT202 did not surpass the performance of [F-18]FLT. We therefore conclude that [(18)f]NFT202 is not a suitable PET ligand for imaging tumor cell proliferation. (c) 2006 Elsevier Inc. All rights reserved.