New approach for the synthesis of [F]fluoroethyltyrosine for cancer imaging: Simple, fast, and high yielding automated synthesis

O-(2-¹⁸F]fluoroethyl)-l-tyrosine (¹⁸F]FET) is one of the first ¹⁸F-labeled amino acids for imaging amino acid metabolism in tumors. This tracer overcomes the disadvantages of ¹⁸F]fluorodeoxyglucose, ¹⁸F]FDG, and ¹¹C]methionine, ¹¹C]MET. Nevertheless, the various synthetic methods providing ¹⁸FFET] exhibit a big disadvantage concerning the necessity of two purification steps during the synthesis including HPLC purification, which causes difficulties in the automation, moderate yields, and long synthesis times >60 min.A new approach for the synthesis of ¹⁸F]FET is developed starting from 2-bromoethyl triflate as precursor. After optimization of the synthesis parameters including the distillation step of ¹⁸F]-FCH₂CH₂Br combined with the final purification of ¹⁸F]FET using a simple solid phase extraction instead of an HPLC run the synthesis ¹⁸F]FET could be significantly simplified, shortened, and improved. The radiochemical yield (RCY) was about 45% (not decay corrected and calculated relative to ¹⁸F]F⁻ activity that was delivered from the cyclotron). Synthesis time was only 35 min from the end of bombardment (EOB) and the radiochemical purity was >99% at the end of synthesis (EOS). Thus, this simplified synthesis for ¹⁸F]FET offers a very good option for routine clinical use.