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.
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.
Authors: Alexander Kroiss; Daniel Putzer; Christian Uprimny; Clemens Decristoforo; Michael Gabriel; Wolfram Santner; Christof Kranewitter; Boris Warwitz; Dietmar Waitz; Dorota Kendler; Irene Johanna Virgolini Journal: Eur J Nucl Med Mol Imaging Date: 2011-01-29 Impact factor: 9.236
Authors: Irene Virgolini; Valentina Ambrosini; Jamshed B Bomanji; Richard P Baum; Stefano Fanti; Michael Gabriel; Nikolaos D Papathanasiou; Giovanna Pepe; Wim Oyen; Clemens De Cristoforo; Arturo Chiti Journal: Eur J Nucl Med Mol Imaging Date: 2010-10 Impact factor: 9.236
Authors: Pedram Heidari; Alicia Szretter; Laura E Rushford; Maria Stevens; Lee Collier; Judit Sore; Jacob Hooker; Umar Mahmood Journal: Am J Nucl Med Mol Imaging Date: 2016-07-06
Authors: Volker H Schartinger; József Dudás; Clemens Decristoforo; Christoph Url; Johannes Schnabl; Georg Göbel; Irene J Virgolini; Herbert Riechelmann; Michael Rasse; Dietmar Waitz; Daniel Putzer Journal: Eur J Nucl Med Mol Imaging Date: 2013-05-18 Impact factor: 9.236