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

• Published in: Inorganic chemistry Vol. 62; no. 50; pp. 20769 - 20776
• Main Authors: Price, Thomas W., Wagner, Laurène, Rosecker, Veronika, Havlíčková, Jana, Prior, Timothy J., Kubíček, Vojtěch, Hermann, Petr, Stasiuk, Graeme J.
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 18-12-2023
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.3c02459

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 K Ga‑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.