Synthesis and stability of S‐(2‐[¹⁸F]fluoroethyl)‐L‐homocysteine for potential tumour imaging

Abstract

The F-18 labelled methionine derivative S-(2-[18 F]fluoroethyl)-L-homocysteine ([ 18 F]FEHCys) was prepared by a one-pot two-step synthesis via the protected S-(2-bromoethyl)-L-homocysteine 1 and S-(2-chloroethyl)-L-homocysteine 2 precursors. The bromoethyl derivative 1 gave higher radiochemical yields (40% at 5 min) at 1001C compared with the chloro-analogue (22% at 1001C in 30 min). However, [18 F]FEHCys was found to be unstable in aqueous systems being transformed to the corresponding hydroxyl derivative within 20 min.

Synthesis of novel halo and tosyloxy nortropane derivatives as efficient precursors for the one-step synthesis of the dopamine transporter PET ligand [18F]FECNT

“…Finally, the oily layer was dried in vacuum to give 0.14 g of 10 as colorless oil, which was then redissolved in acetonitrile and purified by preparative HPLC. The fractions containing the desired product were collected, combined and concentrated to dryness to afford compound 10 (100 mg, 0.25 mmol, 81%) as colorless oil and with purity >99% (HPLC, UV, 220 nm 2β-Carbomethoxy-3β-(4-chlorophenyl)-8-(2-chloroethyl)nortropane (11). (15)].…”

“…Bromo-group is another possible leaving group, and bromo-bearing precursors for fluorine-18-labeling have been described. 11 Chloro-group is much less reactive, especially when compared with the tosyloxymoiety and bromine atom, but provides a higher-stability of compounds containing this halogen. 12 Chloro-precursor has moreover been used for one-step radiosynthesis of another tropane-based DAT-radioligand, [ 18 F]LBT-999.…”

“…Compounds 11 and 12 were therefore prepared from the N-mesyloxy-derivative 10 by nucleophilic substitution reaction using chloride and bromide, respectively, and were obtained in 75% and 73% yield (Scheme 3). Both halogenated compounds (11,12) were obtained with purities exceeding 98% (HPLC -method A).…”

Methods for 11C‐ and 18F‐labelling of amino acids and derivatives for positron emission tomography imaging

“…After this successful strategy of relatively easy 18 F‐labelling of amino acids for tumour imaging was demonstrated with the synthesis and application of [ 18 F]FET, it was also transferred to other [ 18 F]fluoroalkyl and [ 18 F]fluoroacyl derivatives of natural amino acids. This includes O ‐[ 18 F]fluoropropyl‐ l ( d )‐tyrosine, O ‐[ 18 F]fluoromethyl‐ l ( d )‐tyrosine, 3‐(2‐[ 18 F]fluoroethyl)tyrosine, 3‐(3‐[ 18 F]fluoropropyl)tyrosine, O ‐methyl‐[3‐(2‐[ 18 F]fluoroethyl)]‐tyrosine, O ‐methyl‐[3‐(3‐[ 18 F]fluoropropyl)]tyrosine, 5‐(2‐[ 18 F]fluoroethoxy)‐ l ‐tryptophan, O ‐(2‐[ 18 F]fluoroethyl)‐α‐methyltyrosine, O ‐(2‐[ 18 F]fluoroethyl)‐2‐ l ‐azatyrosine, O ‐(2‐[ 18 F]fluoroethyl)‐ l ‐tyrosineamide, N 5 ‐[ 18 F]fluoroacetylornithine, S ‐(2‐[ 18 F]fluoroethyl)‐ l ‐homocysteine, S ‐(2‐[ 18 F]fluoroethyl)‐ l ‐methionine, S ‐(3‐[ 18 F]fluoropropyl)homocysteine, 2‐amino‐3‐(2‐[ 18 F]fluoromethylphenyl)‐propionic acid, 2‐amino‐3‐(4‐[ 18 F]fluoromethyl‐phenyl)‐propionic acid, 4‐(2‐[ 18 F]fluoroethyl)‐ l ‐phenylalanine, 4‐(3‐[ 18 F]fluoropropyl)‐ l ‐phenylalanine, 4‐(2‐[ 18 F]fluoroethyl)‐ d ‐phenylalanine and (2S,4R)‐4‐(3‐[ 18 F]fluoropropyl)‐glutamic acid . The synthesis of 2‐(2‐[ 18 F]fluoro‐4‐nitrobenzamido)‐3‐methylbutanoic acid is an example of an acylation reaction.…”

Intriguing cellular processing of a fluorinated amino acid during protein biosynthesis in Escherichia coli

“…This known analogue, L-monofluoroethionine (L-MFE, S-(2-fluoroethyl)-L-homocysteine), the [ 18 F] congener of which has been reported to be potentially useful in tumour imaging, was therefore synthesized and further investigated in this context (ESI Methods; Scheme S1 †). 32,35,36 L-MFE has been reported to be hydrolyzed in D 2 O exclusively to S-(2-hydroxyethyl)-L-homocysteine (L-HEHC) relatively slowly with complete hydrolysis not being observed even after 7 days, although additional studies in H 2 O indicated reduced stability. 32 In our hands, L-MFE was indeed found to be acceptably stable with similar results being obtained in D 2 O with only L-HEHC detected as a degradation product.…”