Gallium-68 (68Ga) 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 68Ga by the amino acid based tripodal chelate H3Dpaa, and two bifunctional derivatives, H3Dpaa.dab and H4Dpaa.ga, under a range of conditions with particular emphasis on the rapid complexation of 68Ga at pH 7.4. 100 μM H3Dpaa achieved a radiochemical yield of 95% at pH 7.4 in 5 minutes at 37 °C. The bifunctional derivatives H4Dpaa.ga and H3Dpaa.dab achieved 94% and 84% radiochemical yields, respectively, under the same conditions. The resulting Ga(iii) complexes show thermodynamic stabilities of log KGaDpaa = 18.53, log KGaDpaa.dab = 22.08, log KGaDpaa.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 68Ga under physiological conditions.

Advanced Theranostic Nanostructures Lab International Iberian Nanotechnology Laboratory Av Mestre José Veiga s n 4715 330 Braga Portugal

Chemistry School of Mathematical and Physical Sciences University of Hull Cottingham Road Hull HU6 7RX UK

Department of Inorganic Chemistry Faculty of Science Charles University Hlavova 2030 12840 Prague 2 Czech Republic

School of Life Sciences Department of Biomedical Sciences University of Hull Cottingham Road Hull HU6 7RX UK

School of Life Sciences Department of Biomedical Sciences University of Hull Cottingham Road Hull HU6 7RX UK and Positron Emission Tomography Research Centre University of Hull Cottingham Road Hull HU6 7RX UK

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

Bn2DT3A, a Chelator for 68Ga Positron Emission Tomography: Hydroxide Coordination Increases Biological Stability of [68Ga][Ga(Bn2DT3A)(OH)]