Bn 2 DT3A , a Chelator for 68 Ga Positron Emission Tomography: Hydroxide Coordination Increases Biological Stability of [ 68 Ga][Ga(Bn 2 DT3A)(OH)] .

The chelator Bn ₂ DT3A was used to produce a novel ⁶⁸ Ga complex for positron emission tomography (PET). Unusually, this system is stabilized by a coordinated hydroxide in aqueous solutions above pH 5, which confers sufficient stability for it to be used for PET. Bn ₂ DT3A complexes Ga ³⁺ in a hexadentate manner, forming a mer-mer complex with log K ([Ga( Bn ₂ DT3A )]) = 18.25. Above pH 5, the hydroxide ion coordinates the Ga ³⁺ ion following dissociation of a coordinated amine. Bn ₂ DT3A radiolabeling displayed a pH-dependent speciation, with [ ⁶⁸ Ga][Ga( Bn ₂ DT3A )(OH)] ^- being formed above pH 5 and efficiently radiolabeled at pH 7.4. Surprisingly, [ ⁶⁸ Ga][Ga( Bn ₂ DT3A )(OH)] ^- was found to show an increased stability in vitro (for over 2 h in fetal bovine serum) compared to [ ⁶⁸ Ga][Ga( Bn ₂ DT3A )]. The biodistribution of [ ⁶⁸ Ga][Ga( Bn ₂ DT3A )(OH)] ^- in healthy rats showed rapid clearance and excretion via the kidneys, with no uptake seen in the lungs or bones.