Fully automated peptide radiolabeling from [¹⁸F]fluoride

The biological properties of receptor-targeted peptides have made them popular diagnostic imaging and therapeutic agents. Typically, the synthesis of fluorine-18 radiolabeled receptor-targeted peptides for positron emission tomography (PET) imaging is a time consuming, complex, multi-step synthetic process that is highly variable based on the peptide. The complexity associated with the radiolabeling route and lack of robust automated protocols can hinder translation into the clinic. A fully automated batch production to radiolabel three peptides (YGGFL, cRGDyK, and Pyr-QKLGNQWAVGHLM) from fluorine-18 using the ELIXYS FLEX/CHEM® radiosynthesizer in a two-step process is described. First, the prosthetic group, 6-[¹⁸F]fluoronicotinyl-2,3,5,6-tetrafluorophenyl ester ([¹⁸F]FPy-TFP) was synthesized and subsequently attached to the peptide. The [¹⁸F]FPy-peptides were synthesized in 13-26% decay corrected yields from fluorine-18 with high molar activity 1-5 Ci μmol^-1 and radiochemical purity of >99% in an overall synthesis time of 97 ± 3 minutes.