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

Abstract

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 K_GaDpaa = 18.53, log K_GaDpaa.dab = 22.08, log K_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 ⁶⁸Ga under physiological conditions.