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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

Authors

  • André F. Martins,

    1. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal
    2. Center of Neurosciences and Cell Biology, Largo Marquês de Pombal, University of Coimbra, Portugal
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    • These authors have contributed equally.

  • M. I. M. Prata,

    1. IBILI, Faculty of Medicine, University of Coimbra, Portugal
    2. ICNAS, University of Coimbra, Portugal
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  • S. P. J. Rodrigues,

    1. Department of Chemistry, Faculty of Sciences and Technology, University of Coimbra, Portugal
    2. Coimbra Chemistry Center, Rua Larga, University of Coimbra, Coimbra, Portugal
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  • Carlos F. G. C. Geraldes,

    Corresponding author
    1. Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, Coimbra, Portugal
    2. Center of Neurosciences and Cell Biology, Largo Marquês de Pombal, University of Coimbra, Portugal
    • Coimbra Chemistry Center, Rua Larga, University of Coimbra, Coimbra, Portugal
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  • P. J. Riss,

    1. The Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, UK
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    • These authors have contributed equally.

  • A. Amor-Coarasa,

    1. Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany
    2. Florida International University, Department of Biomedical Engineering, Miami, Florida, USA
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  • C. Burchardt,

    1. Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany
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  • C. Kroll,

    1. Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany
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  • F. Roesch

    1. Institute of Nuclear Chemistry, Johannes Gutenberg-University, Mainz, Germany
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Correspondence to: Carlos F. G. C Geraldes, Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, PO Box 3046, 3001-401 Coimbra, Portugal. E-mail: geraldes@ci.uc.pt

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 (1H and 71 Ga NMR), radiochemical, mass spectrometry and theoretical modeling studies on the Ga3+/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 Ga3+ and that this interaction depends on the relative Ga3+: 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 Ga3+ by the hydroxyl and adjacent ring nitrogen of HEPES is proposed on the basis of 1H NMR shifts induced by Ga3+ and theoretical modeling studies. Copyright © 2013 John Wiley & Sons, Ltd.

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