Copper, gallium and zirconium positron emission tomography imaging agents: The importance of metal ion speciation

Positron emission tomography (PET) is a medical diagnostic imaging technique that requires administration of a β+-emitting radiotracer to a patient. Metal-based PET radiotracers have become increasingly used in both preclinical and clinical settings in recent years, particularly those incorporating the β+-emitting isotopes of copper, gallium and zirconium. The synthesis of metal-based PET imaging agents with high radiochemical yields and purities requires careful consideration of the speciation of the metal ions in the presence of aqueous buffers and the physiological environment. This review discusses aspects of copper, gallium and zirconium metal ion speciation of relevance to the design and synthesis of radiopharmaceuticals.