2-[18F]Fluoro-L-thymidine(FLT)

The level of proliferation is a key parameter for characterisation of neoplastic lesions. DNA synthesis is the process that is most reliably associated with proliferation. Thymidine has also been successfully labelled with ¹¹C, and the tracer uptake is directly related to cell proliferation. However, use of ¹¹C-thymidine is hampered by the short isotope half-life, the difficult radiosynthesis and the presence of circulating radiolabelled metabolites. Several alternative compounds, labelled with ¹⁸F, have thus been proposed, including 3’-deoxy-3’-[¹⁸F]-fluorothymidine (FLT). Nucleosides, including FLT, enter the cells by facilitated diffusion and by a carrier-mediated mechanism. Once inside the cell, nucleosides are phosphorylated. Although four kinases are involved in the nucleoside metabolism, FLT is only handled by thymidine kinase TK1. TK1 expression is strictly controlled in normal cells and is only enhanced in the late G1 phase and the S phase. It is much higher, by up to 15-fold, in tumour cells.

Some Applications of [18F]-3’-Fluoro-3’-Deoxy-L-Thymidine [FLT]