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

• Published in: Nuclear medicine communications Vol. 28; no. 11; p. 870
• Main Authors: Decristoforo, Clemens, Knopp, Roger, von Guggenberg, Elisabeth, Rupprich, Marco, Dreger, Thorsten, Hess, Andre, Virgolini, Irene, Haubner, Roland
• Format: Journal Article
• Language: English
• Published: England 01.11.2007
• Subjects: 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
• ISSN: 0143-3636
• DOI: 10.1097/MNM.0b013e3282f1753d

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. 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. 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. 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.