Asymmetric Synthesis of Carbon-11 Labelled α-Amino Acids for PET

Abstract

For PET applications in oncological and neurological diagnostics, amino acids have been studied both clinically and pre-clinically during the last 35 years. Nowadays two applications of labelled amino acids for visualisation of tumours attract the main attention: [11C] or [18F]amino acids as substrates of specific membrane transport systems or in vivo measurement of protein synthesis rate. In this review we focussed on 11C-labelled amino acids, since synthetic approaches to [18F]amino acids have been extensively reviewed in the literature. Most of optically pure 11C-labelled amino acids (except [11C]methionine) have been prepared via low-yield non-reliable synthetic procedures. Low availability hampers their evaluation as biological probes. The first synthesis of racemic [11C]lactic acid as an [11C]amino acid precursor was published in 1941. It took more than thirty years to develop the first synthesis of a racemic [11C]amino acid, it was published in 1973. Early examples of asymmetric synthesis of [11C]amino acids led to relatively low enantiomeric excess, up to 82%. Amino acids synthons developed by groups led by Oppolzer, Seebach, Belokon and Horwell allowed highly stereospecific preparation of [11C]amino acids. Enzymatic and biotechnological approaches, catalytic [11C]alkylation of achiral glycine synthons or catalytic hydrogenation of [11C]precursors have not resulted in any practically useful syntheses yet. The importance for PET using new α-substituted amino acids is briefly discussed. Keywords: Amino acids, Asymmetric synthesis, Carbon-11, Neurotransmitters, Positron emission tomography, Radiolabelling, Tumour.