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

Abstract

2-[ 18F]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-[ 18F]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 [ 18F]F 2, which was prepared via the 18O(p,n) 18F nuclear reaction. 2-[ 18F]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-[ 18F]fluoro- l-dopa, determined with an analogous precursor and non-radioactive fluorine under identical conditions, amounted to 42.7±1.6% and 60.2±2.8%, respectively.