title: Spectroscopic, radiochemical, and theoretical studies of the Ga3+-N-2-hydroxyethyl piperazine-N'-2-ethanesulfonic acid (HEPES buffer) system: evidence for the formation of Ga3+ - HEPES complexes in (68) Ga labeling reactions.
abstract: Recent reports have claimed a superior performance of HEPES buffer in comparison to alternative buffer systems for (67/68) Ga labeling in aqueous media. In this paper we report spectroscopic ((1) H and (71) Ga NMR), radiochemical, mass spectrometry and theoretical modeling studies on the Ga(3+)/HEPES system (HEPES = N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid) performed with the aim of elucidating a potential contribution of HEPES in the (68/67) Ga radiolabeling process. Our results demonstrate that HEPES acts as a weakly but competitive chelator of Ga(3+) and that this interaction depends on the relative Ga(3+): HEPES concentration. A by-product formed in the labeling mixture has been identified as a [(68) Ga]Ga(HEPES) complex via chromatographic comparison with the nonradioactive analog. The formation of this complex was verified to compete with [(68) Ga]Ga(NOTA) complexation at low NOTA concentration. Putative chelation of Ga(3+) by the hydroxyl and adjacent ring nitrogen of HEPES is proposed on the basis of (1)H NMR shifts induced by Ga(3+) and theoretical modeling studies.
authors.affiliation: Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, PO Box 3046, 3001-401 Coimbra, Portugal.
authors.forename: André F
authors.initials: AF
authors.lastname: Martins
authors.forename: M I M
authors.initials: MI
authors.lastname: Prata
authors.forename: S P J
authors.initials: SP
authors.lastname: Rodrigues
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
authors.forename: P J
authors.initials: PJ
authors.lastname: Riss
authors.forename: A
authors.initials: A
authors.lastname: Amor-Coarasa
authors.forename: C
authors.initials: C
authors.lastname: Burchardt
authors.forename: C
authors.initials: C
authors.lastname: Kroll
authors.forename: F
authors.initials: F
authors.lastname: Roesch
mesh_terms: D003198:Computer Simulation; D003287:Contrast Media / Q000138:chemical synthesis*; D015195:Drug Design; D005710:Gallium Radioisotopes / Q000737:chemistry*; D006531:HEPES / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008956:Models, Chemical; D019275:Radiopharmaceuticals / Q000138:chemical synthesis; D013057:Spectrum Analysis
chemical_list: D003287:Contrast Media; D005710:Gallium Radioisotopes; D019275:Radiopharmaceuticals; D006531:HEPES