Automation for Optimised Production of Fluorine-18-Labelled Radiopharmaceuticals

Most F-18 radiolabelling is currently done by nucleophilic substitution using no-carrier-added [F18]-fluoride. F-18 radionuclide produced in the cyclotron is a poor nucleophile that is unreactive in aqueous media and must undergo a number of processes to maximise reactivity. First it must be isolated from the target material (separation), then dried to remove traces of water (drying) and dissolved in an anhydrous solvent together with the precursor to initiate reaction (labelling). The intermediate labelled product then may need to be hydrolysed (de-protection) and finally, separated from the crude mixture (purification).

An automated radiolabelling module is essential for the development and production of PET radiopharmaceuticals for performing basic functions such as transfer of fluids and heating and stirring. Sounds easy, but in reality the requirements of PET radiochemistry create unique challenges for the automated system. Such challenges are; radiation resistance and chemical compatibility of materials, reliability of control components, size constraints due to the need for shielding, product sterility and safety to the operator.

Advances in computing hardware and software have had a major impact on automation of radiolabelling. Simplified program control and visualization of components and sensors has made the radiochemist's work easier and safer. Modern synthesizer programs incorporate real-time displays of hardware status and trend graphs of various parameters (radioactivity, temperature, pressure) so that the synthesizer is no longer a “black box”.

Finally, miniaturisation of components and more recently the design of “microfluidic reactors” have shown potential for further improving the radiolabelling process.