Moving Metal-Mediated 18F-Fluorination from Concept to Clinic

Positron emission tomography (PET) imaging is a functional medical imaging technique that provides information about how tissues and organs are working at the physiological and biochemical level. PET works by injecting a patient or animal with a radiotracer (a biologically active molecule tagged with positron-emitting radionuclide) and detecting pairs of γ rays resulting from annihilation of the positron emitted by the radiotracer. PET has been used to study, diagnose, and stage diseases in patients, and to support drug discovery programs.1 Because of its excellent imaging properties and ready availability from small-medical cyclotrons, fluorine-18 (18F) is one of the most commonly used PET radionuclides. However, working with radioactive 18F presents unique challenges to PET radiochemists. Most notably, (i) the half-life of 18F is 110 min, which means that the radionuclide needs to be made on demand and used immediately; and (ii) the high levels of radioactivity involved in patient-scale PET tracer syntheses necessitate fully automated synthesis and purification procedures (i.e., all operations are controlled by a computer and not by hand). Due to these requirements, scalable radiofluorination processes must involve the incorporation of 18F at a late stage of the tracer synthesis, with short reaction times (usually ≤30 min), and using operationally simple procedures. These constraints, in combination with limitations imposed by traditional reactions using fluorine-18, mean that certain bioactive molecules have historically proven extremely problematic to radiolabel.