Selective fluorination of m-tyrosine by OF₂

Fluorine-18 labeled aromatic amino acids are routinely used as tracers in positron emission tomography (PET) to study in vivo metabolic processes. The most versatile method for the production of such radiotracers is electrophilic fluorination of the aromatic amino acid with [¹⁸F]F₂, which is most commonly produced by the gas-phase nuclear reaction ¹⁸O(p, n)¹⁸F. Although [¹⁸F]F₂ is the major product, considerable amounts of [¹⁸F]OF₂ (up to 20%) are also produced. Electrophilic fluorination reactions of l-phenylalanine, 3-nitro-l-tyrosine, 4-nitro-dl-phenylalanine, 3,4-dihydroxyphenyl-l-alanine (l-DOPA), 3-O-methyl-l-DOPA, 3,4-dimethoxy-l-phenylalanine, p-tyrosine and o-tyrosine in H₂O and of m-tyrosine in anhydrous HF (aHF), CF₃SO₃H, CF₃COOH, CH₃COOH, HCOOH and H₂O using OF₂ were investigated. Although F₂ is an efficient fluorinating agent in aHF, electrophilic fluorination reactions using OF₂ were shown to be most efficient in less acidic media such as H₂O. In addition, and contrary to reports that OF₂ and F₂ have similar reactivities, m-tyrosine was the only aromatic system studied that was fluorinated by OF₂ and this was optimum in H₂O for the fluorinated m-tyrosine isomers (total yield, 4.35 ± 0.04%). The presence of [¹⁸F]OF₂ byproduct has no significant impact on the fluorination of aromatic amino acids investigated in this study and the subsequent production of their corresponding ¹⁸F-labeled radiotracers for patient use.