Synthesis and evaluation of 3'-[F]fluorothymidine-5'-squaryl as a bioisostere of 3'-[F]fluorothymidine-5'-monophosphate.

The squaryl moiety has emerged as an important phosphate bioisostere with reportedly greater cell permeability. It has been used in the synthesis of several therapeutic drug molecules including nucleoside and nucleotide analogues but is yet to be evaluated in the context of positron emission tomography (PET) imaging. We have designed, synthesised and evaluated 3'-[F]fluorothymidine-5'-squaryl ([F]SqFLT) as a bioisostere to 3'-[F]fluorothymidine-5'-monophosphate ([F]FLTMP) for imaging thymidylate kinase (TMPK) activity.