Synthesis of 2-[18F]fluoro-L-tyrosine via regiospecific fluoro-de-stannylation

2-[F-18]Fluoro-L-tyrosine is a fluorine labelled amino acid, known to be incorporated into newly synthesised proteins, rendering it a potentially suitable tracer to image protein metabolism in vivo using positron emission tomography. For the electrophilic preparation of 2-[F-18]fluoro-L-tyrosine three protected 2-trialkylstannyl tyrosine derivatives have been synthesised for the first time as precursors. While O,N-di-Boc-2-triethylstannyl-L-tyrosine ethylester has proved to be suitable as precursor for radiosynthesis, imidazolidinon-derivatives of 2-triaklylstannyl tyrosine have not because of difficult fast hydrolysis of a phenolic O-methyl protective group. The di-Boc-tin derivative of tyrosine ethylester readily reacted with [F-18]F-2, which was prepared via the O-18(p,n)F-18 nuclear reaction. 2-[F-18]Fluoro-L-tyrosine was isolated after full deprotection with aqueous hydrobromic acid and HPLC purification with activities of 1.41 +/- 0.32 GBq. The isomeric and enantiomeric purity is high (both >99%). The preparation procedure is facile and easy to automate. The chemical yields of this fluoro-de-stannylation reaction as well as of the synthesis of 6-[F-18]fluoro-L-dopa, determined with an analogous precursor and non-radioactive fluorine under identical conditions, amounted to 42.7 +/- 1.6% and 602 +/- 2.8%, respectively. (C) 2002 Elsevier Science Ltd. All rights reserved.