title: How is (68)Ga labeling of macrocyclic chelators influenced by metal ion contaminants in (68)Ge/(68)Ga generator eluates?
abstract: To assess the influence of Zn(2+) , Cu(2+) , Fe(3+) , Al(3+) , Ti(IV) , and Sn(IV)  on incorporation of (68) Ga(3+)  into pendant-arm macrocyclic chelators, the (68) Ga labeling of 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-tris[methyl(2-carboxyethyl)phosphinic acid]) (TRAP), and 1,4,7-triazacyclononane-1-[methyl(2-carboxyethyl)phosphinic acid]-4,7-bis[methyl(2-hydroxymethyl)phosphinic acid] (NOPO), as well as their peptide conjugates, was investigated in the presence of varying concentrations of these metal ions. The (68) Ga labeling yield for carboxylate-type chelators NOTA and DOTA is decreased at lower metal ion contaminant concentrations compared with phosphinate-type chelators TRAP and NOPO. The latter are able to rapidly exchange coordinated Zn(II)  with (68) Ga(3+) , as confirmed by mass spectrometry and (31) P NMR spectroscopy. (68) Ga labeling of Zn(II)  complexes of TRAP and NOPO proceeds as efficient as labeling of neat NOTA; this applies also to the corresponding peptide conjugates of these chelators. This behavior results in substantially improved selectivity for Ga(3+)  and, therefore, in more robust and reliable (68) Ga labeling procedures. In addition, none of the investigated chelators binds (68) Ge, rendering post-labeling purification protocols, for example, solid-phase extraction, a reliable means of removal of (68) Ge contamination from (68) Ga radiopharmaceuticals.
authors.affiliation: Pharmaceutical Radiochemistry, Technische Universität München, Walther-Meißner-Strasse 3, 85748 Garching, Germany.
authors.forename: Jakub
authors.initials: J
authors.lastname: Šimeček
authors.forename: Petr
authors.initials: P
authors.lastname: Hermann
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Johannes
authors.initials: J
authors.lastname: Notni
mesh_terms: D002614:Chelating Agents / Q000737:chemistry*; D005710:Gallium Radioisotopes / Q000737:chemistry*; D005857:Germanium / Q000737:chemistry*; D007553:Isotope Labeling; D047028:Macrocyclic Compounds / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D010721:Phosphinic Acids / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry*
chemical_list: D002614:Chelating Agents; D005710:Gallium Radioisotopes; D047028:Macrocyclic Compounds; D008670:Metals; D010721:Phosphinic Acids; D019275:Radiopharmaceuticals; D005857:Germanium