68Ge/68Ga Generators: Past, Present, and Future

In 1964, first 68Ge/68Ga radionuclide generators were described. Although the generator design was by far not adequate to our today’s level of chemical, radiopharmaceutical and medical expectations, it perfectly met the needs of molecular imaging of this period. 68Ga-EDTA as directly eluted from the generators entered the field of functional diagnosis, in particular for brain imaging. A new type of 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 and opened new pathways of MeIII based radiopharmaceutical chemistry. The impressive success of utilizing 68Ga- DOTA-octreotides and PET/CT instead of e.g., 111In-DTPA-octreoscan and SPECT paved the way not only towards clinical acceptance of this particular tracer for imaging neuroendocrine tracers, but to the realisation of the great potential of the 68Ge/68Ga generator for modern nuclear medicine in general. 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), now ask for further developments – towards the optimization of 68Ge/68Ga generators both from chemical and regulatory points of view. Dedicated chelators may be required to broaden the feasibility of 68Ga labeling of more sensitive targeting vectors and generator chemistry may be adopted to those chelators – or vice versa. This review describes the development and the current status of 68Ge/68Ga radionuclide generators.