A fully automated synthesis for the preparation of 68Ga-labelled peptides

Nucl Med Commun. 2007 Nov;28(11):870-5. doi: 10.1097/MNM.0b013e3282f1753d.


Background: Generator-produced Ga has attracted increasing interest for radiolabelling peptides used in PET applications. So far, the synthesis of Ga-peptide radiopharmaceuticals is mainly based on semi-automated systems. Here we describe a fully automated approach for the synthesis of Ga-labelled peptides.

Method: A commercially available Ga generator was eluted with 0.1 mol . l HCl. Reaction parameters such as buffer conditions, pH range, reaction temperature and time, volume of reaction solution and generator fraction were optimized for labelling DOTA-Tyr-octreotide (DOTATOC). Reaction yields, pH, radiochemical purity, sterility, endotoxins, breakthrough of Ge and final Ge content were determined. A fully automated radiopharmaceutical synthesis device based on a modular concept for remote-controlled processing was developed and evaluated for a number of DOTA-derivatized peptides.

Results: DOTATOC could be labelled in almost quantitative yields by heating 10-50 nmol peptide at pH 3.5-4.0 for 5 min at 95 degrees C in 1.5 ml. Purification using a reversed-phase cartridge was required to avoid any potential Ge breakthrough: final activities of Ge were below 100 Bq . ml. Automated synthesis resulted in overall decay-corrected reaction yields of about 60% within 10 min. Even after 1 year using a 1110 MBq generator more than 130 MBq Ga-DOTATOC could be obtained. Moreover, it was demonstrated that a variety of DOTA-derivatized peptides can be labelled using identical reaction conditions with high yields.

Conclusion: The system described allows the fully automated, efficient and rapid preparation of Ga-DOTA-derivatized peptides. It has been used successfully and reliably for routine preparations in clinical studies.

MeSH terms

  • Automation
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Gallium / chemistry*
  • Germanium / chemistry
  • Indicators and Reagents
  • Isotope Labeling / methods
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Peptides / chemical synthesis*
  • Radioisotopes / chemistry
  • Radiopharmaceuticals / chemical synthesis*
  • Reproducibility of Results
  • Sterilization


  • Indicators and Reagents
  • Organometallic Compounds
  • Peptides
  • Radioisotopes
  • Radiopharmaceuticals
  • Germanium
  • gallium Ga 68 dotatate
  • Gallium