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  • Title: How is (68)Ga labeling of macrocyclic chelators influenced by metal ion contaminants in (68)Ge/(68)Ga generator eluates?
    Author: Šimeček J, Hermann P, Wester HJ, Notni J.
    Journal: ChemMedChem; 2013 Jan; 8(1):95-103. PubMed ID: 23136062.
    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.
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