Selective synthesis of L ‐2‐[18F]fluoro‐alpha‐methylphenylalanine via copper mediated 18F‐fluorination of (mesityl)(aryl)iodonium salt

L ‐2‐[18F]fluoro ‐alpha‐methylphenylalanine (2‐[18F]FAMP) is a promising amino acid tracer for positron emission tomography (PET) imaging, yet the low production yield of direct electrophilic radiofluorination with [18F]F2 necessitates further optimization of the radiolabeling process. This paper describes a 2 ‐step preparation method for L‐2‐[18F]fluoro ‐alpha‐methylphenylalanine (2‐[18F]FAMP) starting from [18F]fluoride.The (Mesityl)(L ‐alpha‐methylphenylalanine)‐2‐iodonium tetrafluoroborate precursors with various protecting groups were prepared. The copper‐mediated18F ‐fluorination of the iodonium salt precursors successfully produced 2‐[18F]FAMP. The highest radio chemical conversion of 57.6% was noted withN‐Piv‐protected (mesityl)(aryl)iodonium salt in the presence of 5 equivalent of Cu (OTf)2. Subsequent deprotection with 57% hydrogen iodide produced 2 ‐[18F]FAMP within 120 min in 21.4 ±11.7% overall radiochemical yield with>95% radiochemical purity and an enantiomeric excess>99%. The obtained 2 ‐[18F]FAMP showed comparable biodistribution profiles in normal mice with that of the carrier ‐added 2‐[18F]FAMP.These results indicate that usefulness of copper mediated18F ‐fluorination for the production of 2‐[18F]FAMP, which would facilitate clinical translation of the promising tumor specific amino acid tracer. Individual facilities could adopt either production method based on radioactivity demand and equipment av...

Source: Journal of Labelled Compounds and Radiopharmaceuticals - March 28, 2020 Category: Biochemistry Authors: Aiko Yamaguchi, Hirofumi Hanaoka, Tetsuya Higuchi, Yoshito Tsushima Tags: RESEARCH ARTICLE Source Type: research