Past, present and future of 68Ge/68Ga generators

68Ga represents one of the very early radionuclides applied to positron emission tomography (PET) imaging at a time when even the wording PET itself was not established. Today it faces a renaissance in terms of new 68Ge/68Ga radionuclide generators, sophisticated 68Ga radiopharmaceuticals, and state-of-the-art clincial diagnoses via positron emission tomography/computed tomography (PET/CT). Thanks to the pioneering achievement of radiochemists in Obninsk, Russia, a new type of 68Ge/68Ga generators became commercially available in the first years of the 21st century. Generator eluates based on hydrochloric acid provided “cationic” 68Ga instead of “inert” 68Ga-complexes, opening new pathways of MeIII based radiopharmaceutical chemistry. Consequently, the last decade has seen a 68Ga rush. Increasing applications of generator based 68Ga radiopharmaceuticals (for diagnosis alone, but increasingly for treatment planning, thanks to the inherent option as expressed by THERANOSTICS, ask for new developments towards the optimisation of 68Ge/68Ga generators both from chemical and regulatory points of view.

► This article describes central aspects of 68Ge/68Ga radionuclide generators.
► It covers the early period represented by EDTA-based generator eluents, until the recent developments of HCl-based eluents providing cationic 68Ga species ready for labeling.
► Several approaches to process the initial eluate are discussed in the context of state-of-the-art radiopharmaceutical chemistry, but also relevant legal aspects related to the level of 68Ge breakthrough.