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. (14th February 2013)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Contrast media & molecular imaging. Volume 8:Number 3(2013:May/Jun.)
• Page Start: 265
• Page End: 273
• Publication Date: 2013-02-14
• Subjects: radiolabeling -- 68 Ga -- PET tracers -- HEPES buffer–Ga3+ interactions -- multinuclear NMR -- theoretical modeling -- mass spectrometry; Diagnostic imaging -- Periodicals; Magnetic resonance imaging -- Periodicals; Contrast media (Diagnostic imaging) -- Periodicals; Contrast Media -- Periodicals; Diagnostic Imaging -- Periodicals; Substances de contraste -- Périodiques; Diagnostics moléculaires -- Périodiques; Imagerie médicale; Substance de contraste; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.0754
• DOI: 10.1002/cmmi.1517
• Languages: English
• ISSNs: 1555-4309

Abstract

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. Copyright © 2013 John Wiley & Sons, Ltd. Abstract : We show by spectroscopic, radiochemical, chromatographic, mass spectrometry and theoretical modelling studies that the HEPES buffer acts as a weakly but competitive chelator of Ga 3+ . This observation explains its superior performance relative to alternative buffer systems for 67/68 Ga radiolabelling in aqueous media.