Synthesis of [F‐18]‐1‐amino‐3‐fluorocyclobutane‐1‐carboxylic acid (FACBC): a PET tracer for tumor delineation

Fluorine-18 labeled 1-amino-3-fluorocyclobutane-1-carboxylic acid (FACBC), a new tumor-avid amino acid, was synthesized for positron emission tomography. [18F]FACBC was prepared with high specific activity by nucleophilic displacement with an overall radiochemical yield of 12% (EOB). Synthesis of the triflate precursor was accomplished in nine steps starting from the reaction of benzyl bromide with epichlorohydrin which gave 1-chloro-2-benzyloxy-3-brompropane. A key step involves conversion of 3-benzyloxy-cyclobutane-1,1-dicarboxylate diamide to a mixture of diastereomeric 2-benzyloxycyclobutane hydantoins. Copyright © 1999 John Wiley & Sons, Ltd.