Inorganic Chemistry of the Tripodal Picolinate Ligand Tpaa with Gallium(III) and Radiolabeling with Gallium-68

Price, Thomas W.; Wagner, Laurène; Rosecker, Veronika; Havlíčková, Jana; Prior, Timothy J.; Kubíček, Vojtěch; Hermann, Petr; Stasiuk, Graeme J.

Abstract

We report here the improved synthesis of the tripodal picolinate chelator Tpaa, with an overall yield of 41% over five steps, in comparison to the previously reported 6% yield. Tpaa was investigated for its coordination chemistry with Ga(III) and radiolabeling properties with gallium-68 (68Ga). The obtained crystal structure for [Ga(Tpaa)] shows that the three picolinate arms coordinate to the Ga(III) ion, fully occupying the octahedral coordination geometry. This is supported by 1H NMR which shows that the three arms are symmetrical when coordinated to Ga(III). Assessment of the thermodynamic stability through potentiometry gives log KGa-Tpaa = 21.32, with a single species being produced across the range of pH 3.5-7.5. Tpaa achieved >99% radiochemical conversion with 68Ga under mild conditions ([Tpaa] = 6.6 μM, pH 7.4, 37 °C) with a molar activity of 3.1 GBq μmol-1. The resulting complex, [68Ga][Ga(Tpaa)], showed improved stability over the previously reported [68Ga][Ga(Dpaa)(H2O)] in a serum challenge, with 32% of [68Ga][Ga(Tpaa)] remaining intact after 30 min of incubation with fetal bovine serum.

Citation

Price, T. W., Wagner, L., Rosecker, V., Havlíčková, J., Prior, T. J., Kubíček, V., …Stasiuk, G. J. (2023). Inorganic Chemistry of the Tripodal Picolinate Ligand Tpaa with Gallium(III) and Radiolabeling with Gallium-68. Inorganic chemistry, 62(50), 20769–20776. https://doi.org/10.1021/acs.inorgchem.3c02459

• Journal Article Type: Article
• Acceptance Date: Sep 13, 2023
• Online Publication Date: Oct 4, 2023
• Publication Date: Oct 18, 2023
• Deposit Date: Dec 20, 2023
• Publicly Available Date: Dec 21, 2023
• Journal: Inorganic Chemistry
• Print ISSN: 0020-1669
• Electronic ISSN: 1520-510X
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 62
• Issue: 50
• Pages: 20769–20776
• DOI: https://doi.org/10.1021/acs.inorgchem.3c02459
• Keywords: Ligands; Mechanisms of action; Radiolabeling; Serum; Stability
• Public URL: https://hull-repository.worktribe.com/output/4445087