Hhox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for Ga Radiopharmaceuticals.

An acyclic hexadentate oxine-derived chelating ligand, Hhox, was investigated as an alternative to current chelators for Ga. The straightforward preparation of Hhox, involving only one or two steps, obviates the synthetic challenges associated with many reported Ga chelators; it forms a Ga complex of great stability (log K = 34.4) with a remarkably high gallium scavenging ability (pGa = -log[Ga] = 28.3, ([Ga] = 1 μM; [L ] = 10 μM; pH 7.4, and 25 °C)). Moreover, Hhox coordinates Ga quantitatively in 5 min at room temperature in ligand concentrations as low as 1 × 10 M, achieving an unprecedented high molar activity of 11 ± 1 mCi/nmol (407 ± 3.7 MBq/nmol) without purification, suggesting prospective kit-based convenience. [Ga(hox)] showed no decomposition in a plasma challenge. Good in vivo stability and fast renal and hepatic clearance of the [Ga(hox)] complex were demonstrated using dynamic positron emission tomography/computed tomography imaging. The intrinsic fluorescence of [Ga(hox)] allowed for direct fluorescence imaging of cellular uptake and distribution, demonstrating the dual-channel detectability and intracellular stability of the metal complex.