The renaissance of the ⁶⁸Ge/⁶⁸Ga radionuclide generator initiates new developments in ⁶⁸Ga radiopharmaceutical chemistry.

⁶⁸Ge/⁶⁸Ga radionuclide generators have been investigated for almost fifty years now, since the cyclotron-independent availability of positron emitting ⁶⁸Ga via the ⁶⁸Ge/⁶⁸Ga system had always attracted researches working in basic nuclear chemistry as well as radiopharmaceutical chemistry. However, it took decades and generations of research (and researchers) to finally approach a reliable level of ⁶⁸Ge/⁶⁸Ga generator designs, adequate to the modern requirements of radiometal labeling chemistry. ⁶⁸Ga radiopharmacy now is awaking from a sort of hibernation. The exciting perspective for the ⁶⁸Ge/⁶⁸Ga generator, now - more than ever, asks for systematic chemical, radiochemical, technological and radiopharmaceutical efforts, to guarantee reliable, highly-efficient and medically approved ⁶⁸Ge/⁶⁸Ga generator systems. The expected future broad clinical impact of ⁶⁸Ga-labelled radiopharmaceuticals - beyond the ⁶⁸Ga-DOTA-octreotide derivatives - for imaging tumors and many organs, on the other hand, identifies the development of sophisticated Ga(III) chelating structures to be a key factor. Today, open chain complexing agents have almost completely been displaced by macrocyclic DOTA and NOTA-derived conjugates. Structures of chelating moieties are being optimized in terms of thermodynamic stability and kinetic inertness, in terms of labeling efficacies at different, even acidic pH, and in terms of synthetic options towards bifunctionality, directed to sophisticated covalent coupling strategies to a variety of biologically relevant targeting vectors. Today, one may expect that the ⁶⁸Ge/⁶⁸Ga radionuclide generator systems could contribute to and facilitate the clinical impact of nuclear medicine diagnoses for PET in a dimension comparable to the established ⁹⁹Mo/⁹⁹(m)Tc generator system for SPECT.