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

[Image: see text] 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.