The B�cherer-Strecker synthesis of d- and l-(1-11C)tyrosine and the in vivo study of l-(1-11C)tyrosine in human brain using positron emission tomography

Abstract

The synthesis of D- and L-(1-11C)tyrosine, starting with 11C-cyanide, is reported. DL-(1-11C)Tyrosine was prepared by the Bücherer-Strecker reaction, from carrier added 11C-cyanide with an incorporation of 80% in 20 min. The isolation of the pure D- and L-amino acid isomers from the enantiomeric mixture was accomplished within 15 min by preparative HPLC using a chiral stationary phase and a phosphate buffer as the mobile phase. Typically, the total synthesis time was 50 min (including purification) from end of trapping of 11C-cyanide, with a radiochemical yield of D- and L-amino acid of 40%-60%. The D- and L-(1-11C)tyrosine were both obtained optically pure, with a carrier added specific activity of 0.3-0.5 Ci/mmol and a radiochemical purity better than 99%. The 11C labelled L-tyrosine was used in an in vivo study in the human brain using positron emission tomography (PET).

Specific transport of 3‐fluoro‐l‐α‐methyl‐tyrosine by LAT1 explains its specificity to malignant tumors in imaging

“…For the synthesis of 3‐fluoro‐ l ‐α‐methyl[carboxyl‐ 14 C]tyrosine ([ 14 C]FAMT), 3‐fluoro‐4‐methoxyphenylacetone as a starting material was purchased from NARD Institute (Amagasaki, Japan). [ 14 C]FAMT was synthesized by Sekisui Medical (Tokyo, Japan) to obtain high specific radioactivity by Bücherer–Strecker reaction . [ 14 C]FAMT was identified by the analysis of 1 H‐nuclear magnetic resonance (AV400M; Bruker Biospin, Rheinstetten, Germany), high performance liquid chromatograph (Agilent 1200) and mass spectrum (LTQXL; Thermo Fisher Scientific, Waltham, MA, USA) .…”

11CO bonds made easily for positron emission tomography radiopharmaceuticals

“…199 Both unnatural amino acids 182 and natural ones have been prepared from [ 11 C]HCN, including [ 11 C- carbonyl ]tyrosine 200 and [ 11 C- carbonyl ]leucine (Fig. 7), 177 both of which are useful tools for imaging l -type amino acid transporter 1 (LAT1), protein synthesis in the brain, and gliomas.…”

Exploring Metabolism In Vivo Using Endogenous 11 C Metabolic Tracers

“…Synthesis of racemic [1- 11 C] L-alanine is most commonly performed via the Strecker synthesis, in which 11 C-CN is incorporated into an aldehyde analog, in this case a bisulfate adduct followed by treatment with ammonium hydroxide(39). Analogous procedures have been performed for [1- 11 C] leucine(40) and [1- 11 C] tyrosine(41). For synthesis/purification of the pure L-enantiomer, several methods have been employed including (1) separation using high performance liquid chromatography (HPLC) on a chiral stationary phase (2) enzymatic resolution (3) use of a chiral auxiliary, usually glycine-derived (4) application of a chiral catalyst, either for selective hydrogenation or alkylation.…”

“…Several neurotransmitters and their precursors have been studied including 11 C L-tyrosine(41), L-DOPA(77), L-tryptophan(31), 5-hydroxy-L-tryptophan(31), 11 C epinephrine(78) and 11 C norepinephrine(79). 11 C epinephrine has been used to study cardiac sympathetic nerve function in the context of heart transplantation, since the latter is associated with decreased sympathetic nerve integrity(80).…”