Chemical Kinetics of Radiolabelling Reactions

The application of chemical kinetics is one of the most powerful and versatile tools for investigating reaction mechanisms in complex mixtures. Kinetic studies are commonplace in traditional synthetic chemistry but are seldom used in radiopharmaceutical sciences. When deriving standard reaction rate laws, the focus is normally placed on calculating the chemical concentration of different species over time. In radiopharmaceutical synthesis, the desired product is one of the radioactive components of the mixture. Reaction conditions are optimised to obtain the radioactive product in the highest activity yield. When short-lived radionuclides are used, radioactive decay during the reaction window means that the maximum activity yield does not necessarily coincide with the chemical or decay-corrected radiochemical yields. To account for this difference in the kinetic models, it is shown how standard integrated rate laws can be modified to incorporate the contribution from radioactive decay. An example is then presented to show how radiochemical kinetics can be used to model complex systems, like [¹⁸ F]FDG radiosynthesis, that involve parallel or competing reactions at the different chemical scales of the radionuclide and substrate. Increased knowledge of reaction rates, and a more wide-spread application of radiochemical kinetics, can facilitate the development of new radiolabelling reactions. Accurate identification of maximum activity yields using kinetic models also has the potential to improve the optimisation and radiochemical efficiency of all current and future radiopharmaceutical syntheses.