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

  • F. Rösch
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 194)


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.


Diethylene Triamine Pentaacetic Acid Diethylene Triamine Pentaacetic Acid Organic Resin Radionuclide Generator Generator Eluate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Ambe S (1988) Germanium-68-gallium-68 generator with alpha-ferric oxide support. Appl Radiat Isot 39:49CrossRefGoogle Scholar
  2. Anger HO, Gottschalk A (1963) Localzation of brain tumors with the positron scintillation camera. JNM 4:326PubMedGoogle Scholar
  3. Arino H, Skraba WJ, Kramer HH (1978) A new 68Ge/68Ga radioisotope generator system. Int J Appl Radiat Isot 29:117CrossRefGoogle Scholar
  4. Asti M, De Pietri G, Fraternali A, Grassi E, Sghedoni R, Fioroni F, Roesch F, Versari A, Salvo D (2008) Validation of 68Ge/68Ga generator processing by chemical purification for routine clinical application of 68Ga-DOTATOC. Nucl Med Biol 35:721PubMedCrossRefGoogle Scholar
  5. Burrows TW (2002) Nuclear data sheets for A = 6.8. Nucl Data Sheets 97:1–127CrossRefGoogle Scholar
  6. Breeman WAP, de Jong M, de Blois E, Bernard BF, Konijnenberg M, Krenning EP (2005) Radiolabelling DOTA-peptides with 68Ga. Eur J Nucl Med 32:478CrossRefGoogle Scholar
  7. Erhardt GJ, Welch MK (1978) A new germanium-68/gallium-68 generator. J Nucl Med 19:925–929Google Scholar
  8. Gleason GI (1960) A positron cow. Int J Appl Radiat Isot 8:90PubMedCrossRefGoogle Scholar
  9. Greene WT, Tucker WD (1961) An improved gallium-68 cow. Int J Appl Radiat Isot 12:62CrossRefGoogle Scholar
  10. Gottschalk A, Anger HO (1964a) The sensivity of the positron scintillation camera for detecting simulated brain tumors with Gallium-68 EDTA. Am J Roentgen 92:174PubMedGoogle Scholar
  11. Gottschalk A, Anger HO (1964b) Letter to the editor. J Nucl Med 5(3):569Google Scholar
  12. Gottschalk A (1996) The early years with Hal Anger. Sem Nucl Med 26(3):171CrossRefGoogle Scholar
  13. Gottschalk A (2004) Hal Anger: Nuclear medicine′s quiet genius. J Nucl Med 45(23): 13 N, 26 NGoogle Scholar
  14. Kopecky P, Mudrová B, Svoboda K (1973) The study of conditions for the preparation and utilization of 68Ge-68Ga generator. Int J Appl Radiat Isot 24:73CrossRefGoogle Scholar
  15. Kopecky P, Mudrová B (1974) 68Ge-68Ga generator for the production of 68Ga in an ionic form. Int J Appl Radiat Isot 25:263CrossRefGoogle Scholar
  16. Lewis RE, Camin LL (1981) Germanium-68/Gallium-68 generator for the one step elution of ionic gallium-68. J Lab Compds Radiopharm 18, 16Google Scholar
  17. Loc′h C, Maziere B, Comar D (1980) A new generator for ionic gallium-68. J Nucl Med 21:171Google Scholar
  18. Malyshev KV, Smirnov VV (1975) Gallium-68 yield from hydrated zirconium oxide-based generators. Sov Radiochim 17:137Google Scholar
  19. McQueen JD, Abbassioun K (1968) Cisternal brain scanning with positron emitting isotopes. J Neurosurg 29(6):597PubMedCrossRefGoogle Scholar
  20. Meyer G-J, Mäcke HR, Schuhmacher J, Knapp WH, Hofmann M (2004) 68Ga-labelled DOTA-derivatised peptide ligands. Eur J Nucl Med 31:1097CrossRefGoogle Scholar
  21. Neirinckx RD, Davis MA (1980) Potential column chromatography for ionic Ga-68 II: Organic ion exchangers as chromatographic supports. J Nucl Med 21:81PubMedGoogle Scholar
  22. Razbash AA, Sevastianov YuG, Krasnov NN, Leonov AI, Pavlekin VE (2005) Germanium-68 row of products. Proceedings of the 5th International Conference on Isotopes, 5ICI, Brussels 25–29 April Medimond, Bologna, pp 147–151Google Scholar
  23. Roesch F, Baum RP (2011) Generator-based PET radiopharmaceuticals for molecular imaging of tumours: On the way to THERANOSTICS. Dalton Trans 40(23):6104–6111CrossRefGoogle Scholar
  24. Roesch F, Riss PJ (2010) The Renaissance of the 68Ge/68Ga radionuclide generator initiates new developments in 68Ga radiopharmaceutical chemistry. Curr Top Med Chem 10(16):1633–1668PubMedGoogle Scholar
  25. Schaer LR, Anger HO, Gottschalk A (1965) Gallium Edetate 68Ga experiences in brain-lesion detection with the positron camera. AMAM 198:139Google Scholar
  26. Schumacher J, Maier-Borst W (1981) A new 68Ge/68Ga radioisotope generator system for production of 68Ga in dilute HCl. Int J Appl Radiat Isot 32:31CrossRefGoogle Scholar
  27. Schönfeld E(1999) 68Ge-68Ga. Comments on evaluation—CEA ISBN 27272 02111 3Google Scholar
  28. Shealy CN, Aronow S, Brownell GL (1964) Gallium-68 as a scanning agent for intracranial lesions. J Nucl Med 5:161PubMedGoogle Scholar
  29. Yano Y, Anger HO (1964) A gallium-68 positron cow for medical use. J Nucl Med 5:484PubMedGoogle Scholar
  30. Zhernosekov KP, Filosofov DV, Baum RP, Aschoff P, Bihl H, Razbash AA, Jahn M, Jennewein M, Rösch F (2007) Processing of generator-produced 68Ga for medical application. J Nucl Med 48:1741PubMedCrossRefGoogle Scholar
  31. Zimmerman RA (1964) The Times They Are a-Changin’. Columbia RecordsGoogle Scholar
  32. Zoller F, Riss PJ, Montforts F-P, Rösch F (2010) Efficient post-processing of aqueous generator eluates facilitates 68Ga-labelling under anhydrous conditions. Radiochim Acta 98(3):157–160CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Institute of Nuclear ChemistryJohannes Gutenberg-UniversityMainzGermany

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