Improved synthesis of [¹⁸F]FS-PTAD as a new tyrosine-specific prosthetic group for radiofluorination of biomolecules

Abstract

A novel prosthetic group, 4-(p-([(18)F]fluorosulfonyl)phenyl)-1,2,4-triazoline-3,5-dione ([(18)F]FS-PTAD) for site-specific radiofluorination of tyrosine residue in small molecules is described. Coupling of [(18)F]FS-PTAD with L-tyrosine, N-acetyl-L-tyrosine methyl amide and phenol as model compounds were achieved in buffered aqueous solution at room temperature, resulting in the corresponding fluorinated tyrosine and phenol derivatives. The total synthesis time including radiosynthesis, HPLC purification and formulation was less than 60 min (n=15) with ≥98% radio chemical purity. An initial in vitro evaluation of [(18)F]FS-PTAD-tyrosine in glioma cell lines revealed moderate uptake.

Keywords: Ene-like reaction; Prosthetic group; Radiofluorination; Tyrosine conjugation; [(18)F]FS-PTAD.