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

doi:10.1002/cmmi.1517

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 journal › Article › peer-review

21 Scopus citations

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 language	English (US)
Pages (from-to)	265-273
Number of pages	9
Journal	Contrast Media and Molecular Imaging
Volume	8
Issue number	3
DOIs	https://doi.org/10.1002/cmmi.1517
State	Published - 2013
Externally published	Yes

Keywords

Mass spectrometry
Multinuclear NMR
PET tracers
Radiolabeling
Theoretical modeling

ASJC Scopus subject areas

Radiology Nuclear Medicine and imaging

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10.1002/cmmi.1517

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Martins, A. F., Prata, M. I. M., Rodrigues, S. P. J., Geraldes, C. F. G. C., Riss, P. J., Amor-Coarasa, A., Burchardt, C., Kroll, C., & Roesch, F. (2013). 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. Contrast Media and Molecular Imaging, 8(3), 265-273. https://doi.org/10.1002/cmmi.1517

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. et al.
In: Contrast Media and Molecular Imaging, Vol. 8, No. 3, 2013, p. 265-273.

Research output: Contribution to journal › Article › peer-review

Martins, AF, Prata, MIM, Rodrigues, SPJ, Geraldes, CFGC, Riss, PJ, Amor-Coarasa, A, Burchardt, C, Kroll, C & Roesch, F 2013, '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', Contrast Media and Molecular Imaging, vol. 8, no. 3, pp. 265-273. https://doi.org/10.1002/cmmi.1517

Martins AF, Prata MIM, Rodrigues SPJ, Geraldes CFGC, Riss PJ, Amor-Coarasa A et al. 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. Contrast Media and Molecular Imaging. 2013;8(3):265-273. doi: 10.1002/cmmi.1517

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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 68Ga labeling reactions",

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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AU - Martins, André F.

AU - Prata, M. I.M.

AU - Rodrigues, S. P.J.

AU - Geraldes, Carlos F.G.C.

AU - Riss, P. J.

AU - Amor-Coarasa, A.

AU - Burchardt, C.

AU - Kroll, C.

AU - Roesch, F.

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