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

Abstract

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 radiolabeling 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.