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.