Radiosynthesis and initial evaluation of [18F]FSPTAD as new tyrosine-specific prosthetic group for radiofluorination of biomolecules

Objectives The aim of this study was to develop a new F-18 prostatic group for rapid and efficient method specific for tyrosine containing peptides and proteins. A novel fluoride-18 prosthetic ligand, 4-(p-([18F]fluorosulfonyl)phenyl)-1,2,4-triazoline-3,5-dione ([18F]FSPTAD), for site-specific labeling of tyrosine residue in small molecules, peptides and proteins was developed. [18F]FSPTAD reacts efficiently and selectively with phenol derivatives such as tyrosine side chain through an ene-like reaction for radiolabeling of proteins for use in positron emission tomography (PET).

Methods An innovative simple procedure to obtain radiofluorinated sulfonyl fluoride by avoiding time-consuming azeotropic drying was applied. The radiosynthesis of [18F]FSPTAD was performed in two steps at room temperature using different solvent (i-PrOH, THF, and MeCN). N-Acetyl-L-tyrosine ethyl ester and small peptide (Tyr-CO-Glu, TUG) were used as model compounds for coupling. [18F]FSPTAD was conjugated with the model compounds under mild aqueous reaction at room temperature and the obtained radiopharmaceuticals were tested for their affinity in human cancer cell lines.

Results [18F]FSPTAD was obtained in 85±2.7% RCY using MeCN at room temperature and a reaction time of 15 min. DBDMH was used as oxidant to yield [18F]FSPTAD in 5 min in quantitative yield. The coupling of [18F]FSPTAD with N-acetyl-L-tyrosine ethyl ester and TUG was achieved in a buffered aqueous solution at room temperature for 5-10 min to give 45±5.6% and 62±4.3% radiochemical yield, respectively. In addition, [18F]FSTPAD-Ty-OH and [18F]FSTPAD-TUG presented tumour affinity.

Conclusions An efficient method for the preparation of new fluoride-18 prosthetic ligand ([18F]FSPTAD) was developed. Moreover, the mild aqueous reaction shows promising radio-conjugation of broad tyrosine containing biomolecules such as small molecules, peptides and proteins.