Mechanistic approach of the difference in hydrolysis rate between the 2- and 4-isomers of no-carrier-added [18F]fluoromethyl-L-phenylalanine

✍ Scribed by Ken Kersemans; John Mertens; Frank De Proft; Paul Geerlings

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: French
• Weight: 159 KB
• Volume: 54
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1852

✦ Synopsis

Abstract

No‐carrier‐added (n.c.a.) 2‐[^18^F]fluoromethyl‐l‐phenylalanine (2‐[^18^F]FMP) was found to be very sensitive to hydrolysis in aqueous solutions. In this paper, the defluorination reaction was studied in detail to elucidate its mechanism. Therefore, besides 2‐[^18^F]FMP and 4‐[^18^F]FMP, 2‐[^18^F]fluoromethyl‐phenethylamine (2‐[^18^F]FMPAM) and 4‐[^18^F]FMPAM were synthesized, both ‘mimetic’ molecules of the decarboxylated amino acid analogues. Radiosynthesis, using a customized Scintomics automatic synthesis hotbox^three^ module, resulted in a high overall yield and a radiochemical purity of >99%. The defluorination rates of all compounds were studied by HPLC. The defluorination rate of 2‐[^18^F]FMLP at 50°C was approximately 300 times faster than that of n.c.a. 4‐[^18^F]FMLP. The defluorination rate of 2‐[^18^F]FMPAM is somewhat lower than of 2‐[^18^F]FMP but still very high in comparison with 4‐[^18^F]FMPAM, which is virtually stable. It allowed to elucidate the reaction mechanism ruled by two distinct intramolecular interactions. First, the hydrogen bond interaction between the amine and the benzylic fluorine weakening the carbon–fluorine bond. Secondly, the formation of a second hydrogen bond between the carboxyl oxygen atom and one of the benzylic hydrogen atoms rendering the benzyl fluoride group even more susceptible to hydrolysis. Copyright © 2010 John Wiley & Sons, Ltd.