Enzymatic Synthesis of Carboxy-11C-Labelled L-Tyrosine, L-DOPA, L-Tryptophan and 5-Hydroxy-L-tryptophan.

Abstract

The multi-enzymatic syntheses of carboxy-11C-labelled L-tyrosine (3), L-DOPA (4), L-tryptophan (5) and 5-hydroxy-L-trytophan (6) via racemic [1-11C]alanine (1) are presented. DL-[1-11C]Alanine was synthesised from [11C]cyanide by reaction with the bisulfite adduct of acetaldehyde and ammonia, and subsequent hydrolysis of the resulting [11C]amino nitrile. The enzymatic reactions were performed using D-amino acid oxidase (D-AAO)/catalase, glutamic-pyruvic transaminase (GPT), and .beta.-tyrosinase (for L-tyrosine and L-DOPA) or tryptophanase (for L-tryptophan and 5-hydroxy-L-tryptophan), in a one-pot reaction. L-[1-11c]Alanine was also synthesised using the reversibility of GPT in combination with D-AAO. Total synthesis time was ca. 50 min, counted from the start of synthesis of hydrogen [11C]cyanide, obtained from [11C]carbon dioxide. Decay corrected radiochemical yields of the aromatic amino acids were 45-60%, basal on [11C]cyanide, with radiochemical purities higher than 98%. The specific radioactivities of the amino acids were in the order of 0.4-2.0 GBq .mu.mol-1. The enantiomeric purities were determined by HPLC, after derivatisation with N-(5-fluoro-2,4-dinitrophenyl)-L-alaninamide to the corresponding diastereomers, to be higher than 99% L. In a typical run starting with 1.2 GBq hydrogen [11C]cyanide, 150 MBq 5-hydroxy-L-tryptophan was obtained within 45 min.