Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH

Kubicek, Vojtech; Bohmova, Zuzana; Price, Thomas W.; Gallo, Juan; Kubíček, Vojt?ch; Böhmová, Zuzana; Prior, Timothy J.; Greenman, John; Hermann, Petr; Stasiuk, Graeme J.

Abstract

Gallium-68 ( 68 Ga) has been the subject of increasing interest for its potential in the production of radiotracers for diagnosis of diseases. In this work we report the complexation of 68 Ga by the amino acid based tripodal chelate H 3 Dpaa, and two bifunctional derivatives, H 3 Dpaa.dab and H 4 Dpaa.ga, under a range of conditions with particular emphasis on the rapid complexation of 68 Ga at pH 7.4. 100 μM H 3 Dpaa achieved a radiochemical yield of 95% at pH 7.4 in 5 minutes at 37 °C. The bifunctional derivatives H 4 Dpaa.ga and H 3 Dpaa.dab achieved 94% and 84% radiochemical yields, respectively, under the same conditions. The resulting Ga(iii) complexes show thermodynamic stabilities of logK GaDpaa = 18.53, logK GaDpaa.dab = 22.08, logK GaDpaa.ga = 18.36. Unfortunately, the resulting radiolabelled species do not present sufficient serum stability for in vivo application. Herein we show a flexible synthesis for bifunctional chelators based on amino acids that rapidly complex 68 Ga under physiological conditions.

Citation

Kubicek, V., Bohmova, Z., Price, T. W., Gallo, J., Kubíček, V., Böhmová, Z., Prior, T. J., Greenman, J., Hermann, P., & Stasiuk, G. J. (2017). Amino acid based gallium-68 chelators capable of radiolabeling at neutral pH. Dalton Transactions : an international journal of inorganic chemistry, 46(48), 16973-16982. https://doi.org/10.1039/c7dt03398b

• Journal Article Type: Article
• Acceptance Date: Nov 16, 2017
• Publication Date: Nov 17, 2017
• Deposit Date: Feb 13, 2018
• Publicly Available Date: Nov 18, 2018
• Journal: Dalton Transactions
• Print ISSN: 1477-9226
• Electronic ISSN: 1477-9234
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 46
• Issue: 48
• Pages: 16973-16982
• DOI: https://doi.org/10.1039/c7dt03398b
• Keywords: Inorganic Chemistry
• Public URL: https://hull-repository.worktribe.com/output/517356
• Additional Information: : This document is Similarity Check deposited; : Supplementary Information; : Crystal Structure Data; : Juan Gallo (ORCID); : Vojtěch Kubíček (ORCID); : Vojtěch Kubíček (ResearcherID); : Timothy J. Prior (ORCID); : John Greenman (ORCID); : Petr Hermann (ORCID); : Petr Hermann (ResearcherID); : Graeme J. Stasiuk (ORCID); : Single-blind; : Received 12 September 2017; Accepted 16 November 2017; Accepted Manuscript published 17 November 2017; Advance Article published 27 November 2017; Version of Record published 12 December 2017
• Contract Date: Feb 13, 2018