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

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 ( 68 Ga). 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 1 H 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 68 Ga 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, [ 68 Ga][Ga( Tpaa )], showed improved stability over the previously reported [ 68 Ga][Ga( Dpaa )(H 2 O)] in a serum challenge, with 32% of [ 68 Ga][Ga( Tpaa )] remaining intact after 30 min of incubation with fetal bovine serum.