Optimal buffer choice of the radiosynthesis of 68Ga–Dotatoc for clinical application

Abstract

Although the use of HEPES, acetate and succinate as buffering substances yielded comparable results, only acetate is currently recognized as a substance for pharmaceutical use and also for human use. Therefore, acetate buffer should be used for (68)Ga-Dotatoc synthesis. The semi-automated system allowed for a shorter radiosynthesis time, thereby increasing the overall yield.

Optimization of Hapten-Peptide Labeling for Pretargeted ImmunoPET of Bispecific Antibody Using Generator-Produced 68Ga

“…Because gallium exists in various forms based on the pH and concentration (16), our goal was to retain the pH near 3.0, which is lower than most other 68 Ga-DOTApeptides (6,10,(17)(18)(19). For example, Bauwens et al found labeling efficiencies or more than 90% for 68 Ga-DOTATOC using 1 M HEPES, pH 3.75, whereas with 0.5 M sodium succinate, pH approximately 4.0, labeling efficiencies suffered when 10 mg of the peptide was used (19). IMP288 labeling was always performed with less than 10 mg, and at pH 3.7 and 4.6, recovery from analytic RP-HPLC was low, but better recoveries were possible at the lower pH.…”

68Ga-labeled DOTA-Peptides and 68Ga-labeled Radiopharmaceuticals for Positron Emission Tomography: Current Status of Research, Clinical Applications, and Future Perspectives

“…Therefore, all current clinically applied 68 Ga-labeled pharmaceuticals are prepared on site through a so-called magisterial preparation. [21][22][23] Here we give an overview of the state of current knowledge and research of many 68 Ga-labeled pharmaceuticals of the last decade, with focus on the application of 68 Ga-labeled pharmaceuticals for imaging receptor-mediated processes.…”

Feasibility and availability of 68Ga-labelled peptides

“…Cation exchange purification HEPES, water for injection HCl concentration <1 M Presence of acetone, formation of mesityloxide [20], [37], [38] Anion exchange purification HEPES, acetate All types Use of concentrated HCl (5.5 M) [31], [32], [36] Fractionation Acetate HCl concentration <1 M 68 Ge breakthrough [21], [33] attraction towards sophisticated automated systems as we have experienced over the last years, may be reconsidered. The possibility of straightforward and rapid radiolabelling at room temperature and labelling at very low pH as recently described for a triazacyclononane-based bifunctional phosphinate [42] could lead to considerable simplification allowing less cost-intensive approaches.…”

“…The major parameters to achieve this goal in case of DOTAderivatized peptides have been summarized [21]. The possibility of quantitative incorporation of 68 Ga into microgram amounts of DOTA-derivatized peptides is a major advantage of 68 Ga over 18 F. It is mainly determined by pH, level of metal contaminants, temperature and the buffer system employed [36]. 68 Ga emits not only gamma rays, but also high-energy positrons, that add considerably to the local radiation dose to operators.…”