[¹⁸F]FET-βAG-TOCA: The Design, Evaluation and Clinical Translation of a Fluorinated Octreotide

The success of Lutathera™ ([¹⁷⁷Lu]Lu-DOTA-TATE) in the NETTER-1 clinical trial as a peptide receptor radionuclide therapy (PRRT) for somatostatin receptor expressing (SSTR) neuroendocrine tumours (NET) is likely to increase the demand for patient stratification by positron emission tomography (PET). The current gold standard of gallium-68 radiolabelled somatostatin analogues (e.g., [⁶⁸Ga]Ga-DOTA-TATE) works effectively, but access is constrained by the limited availability and scalability of gallium-68 radiopharmaceutical production. The aim of this review is three-fold: firstly, we discuss the peptide library design, biological evaluation and clinical translation of [¹⁸F]fluoroethyltriazole-βAG-TOCA ([¹⁸F]FET-βAG-TOCA), our fluorine-18 radiolabelled octreotide; secondly, to exemplify the potential of the 2-[¹⁸F]fluoroethylazide prosthetic group and copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry in accessing good manufacturing practice (GMP) compatible radiopharmaceuticals; thirdly, we aim to illustrate a framework for the translation of similarly radiolabelled peptides, in which in vivo pharmacokinetics drives candidate selection, supported by robust radiochemistry methodology and a route to GMP production. It is hoped that this review will continue to inspire the development and translation of fluorine-18 radiolabelled peptides into clinical studies for the benefit of patients.