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

The chelator Bn2DT3A was used to produce a novel 68Ga 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. Bn2DT3A complexes Ga3+ in a hexadentate manner, forming a mer-mer complex with log K([Ga(Bn2DT3A)]) = 18.25. Above pH 5, the hydroxide ion coordinates the Ga3+ ion following dissociation of a coordinated amine. Bn2DT3A radio-labeling displayed a pH-dependent speciation, with [68Ga][Ga-(Bn2DT3A)(OH)]- being formed above pH 5 and efficiently radiolabeled at pH 7.4. Surprisingly, [68Ga][Ga(Bn2DT3A)-(OH)]- was found to show an increased stability in vitro (for over 2 h in fetal bovine serum) compared to [68Ga][Ga-(Bn2DT3A)]. The biodistribution of [68Ga][Ga(Bn2DT3A)(OH)]- in healthy rats showed rapid clearance and excretion via the kidneys, with no uptake seen in the lungs or bones.