Synthesis and Application\nof 1‑[<sup>18</sup>F]Fluoro-4-isothiocyanatobenzene for Radiofluorination\nof Peptides\nin Aqueous Medium

Conjugation of radiofluorinated prosthetic groups to\nprimary amines\nof peptides in an aqueous medium is still considerably challenging.\nHerein, we report a one-pot cascade synthesis of 1-[<sup>18</sup>F]fluoro-4-isothiocyanatobenzene\n([<sup>18</sup>F]<b>2d</b>), an isothiocyanate-functionalized\nprosthetic group for radiolabeling of various peptides in aqueous\nmedium. The developed compound [<sup>18</sup>F]<b>2d</b> was\nsynthesized in >99% radiochemical purity with 22.9 ± 3.8%\n(n\n= 12) decay-corrected yield having molar activity of 0.65 ± 0.19\n(n = 12) GBq/μmol. Various clinically important peptides including\nprostate-specific membrane antigen vector, octreotide acetate, biotin\nanalogue, Arg-Gly-Asp analogue, and bradykinin were successfully conjugated\nwith [<sup>18</sup>F]<b>2d</b> in an aqueous medium in a good\nto moderate radiochemical yield. The overall synthesis of [<sup>18</sup>F]<b>2d</b> and its conjugation with a peptide take around\n155 min, including purification.