Full automation of 68Ga labelling of DOTA-peptides including cation exchange prepurification

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

“…39 More detailed data regarding competitions, impurities, and kinetics of labeling DOTApeptides with 68 Ga were described previously. 18,35 Chemistry of eluate concentration and purification of TiO 2 -based generators was recently summarized by Ocak et al 13 Briefly, there are 3 different methods of purification and/or concentration of 68 Ga: (1) by fractionated elution, (2) by anion chromatography, and (3) by cation chromatography. Fractionated elution results in a ready-to-use eluate containing approximately 80% of the elutable 68 Ga activity.…”

“…Second, 68 Ge/ 68 Ga generators have been developed that produce suitable eluates for labeling that can be converted into a 68 Galabeled pharmaceutical for PET studies. 8,[10][11][12][13][14][15][16][17] Third, there are many DOTA-peptides that can be labeled with 68 Ga. Fourth, a variety of monofunctional and bifunctional chelators have been developed that allow the formation of stable 68 Ga 3ϩ complexes and convenient coupling to biomolecules. Fifth, the availability of PET radiolabeled pharmaceuticals by the introduction of 68 Ga in radiopharmacy, independent of an on-site cyclotron, opened new applications and possibilities.…”

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.…”

“…Today most major suppliers of radiosynthesis modules provide systems for 68 Galabelling of peptides. They differ in the postprocessing method employed and are either based on fixed-tubing systems [33,38,39] or, more recently, on single-use cassettes [40] with pharmaceutical advantages in terms of cross-contamination and aseptic handling; however, their costs are higher. These systems provide reliably high yields of typically >60%, in short times.…”

“…The open questions related to these data are clear: What happens in the case of intravenous injection? Cyclotron Co, Obninsk, Russia TiO 2 0.1 M HCl [21], [31], [32], [37] Eckert & Ziegler, Berlin, Germany TiO 2 0.1 M HCl [38], [40] University of Heidelberg, Germany Pyrogallol-formaldehyde resin 5.5 M HCl [5], [31] ITG Isotope Technologies, Garching, Germany Germanium-specific resin 0.05 M HCl [19] In what chemical form will 68 Ge be present in the event of a generator breakthrough? Can it be assumed that 68 Ga produced in situ in organs and tissues will have the same biokinetics as intravenously administered gallium?…”