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 68Ga labeling reactions

André F. Martins, M. I.M. Prata, S. P.J. Rodrigues, Carlos F.G.C. Geraldes, P. J. Riss, A. Amor-Coarasa, C. Burchardt, C. Kroll, F. Roesch

Research output: Contribution to journalArticle

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Abstract

Recent reports have claimed a superior performance of HEPES buffer in comparison to alternative buffer systems for 67/68Ga labeling in aqueous media. In this paper we report spectroscopic (1H and 71Ga 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 68/67Ga 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 [68Ga]Ga(HEPES) complex via chromatographic comparison with the nonradioactive analog. The formation of this complex was verified to compete with [68Ga]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.

Original languageEnglish (US)
Pages (from-to)265-273
Number of pages9
JournalContrast Media and Molecular Imaging
Volume8
Issue number3
DOIs
StatePublished - Jan 1 2013
Externally publishedYes

Fingerprint

HEPES
Buffers
Theoretical Models
piperazine
ethane sulfonate
Chelating Agents
Hydroxyl Radical
Mass Spectrometry
Nitrogen

Keywords

  • Mass spectrometry
  • Multinuclear NMR
  • PET tracers
  • Radiolabeling
  • Theoretical modeling

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

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 68Ga labeling reactions. / Martins, André F.; Prata, M. I.M.; Rodrigues, S. P.J.; Geraldes, Carlos F.G.C.; Riss, P. J.; Amor-Coarasa, A.; Burchardt, C.; Kroll, C.; Roesch, F.

In: Contrast Media and Molecular Imaging, Vol. 8, No. 3, 01.01.2013, p. 265-273.

Research output: Contribution to journalArticle

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abstract = "Recent reports have claimed a superior performance of HEPES buffer in comparison to alternative buffer systems for 67/68Ga labeling in aqueous media. In this paper we report spectroscopic (1H and 71Ga 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 68/67Ga 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 [68Ga]Ga(HEPES) complex via chromatographic comparison with the nonradioactive analog. The formation of this complex was verified to compete with [68Ga]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.",
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