Visualizing Kinetically Robust Co^III₄L₆ Assemblies in Vivo: SPECT Imaging of the Encapsulated [^99mTc]TcO₄^– Anion

Noncovalent encapsulation is an attractive approach for modifying the efficacy and physiochemical properties of both therapeutic and diagnostic species. Abiotic self-assembled constructs have shown promise, yet many hurdles between in vitro and (pre)­clinical studies remain, not least the challenges associated with maintaining the macromolecular, hollow structure under nonequilibrium conditions. Using a kinetically robust Co^III₄L₆ tetrahedron we now show the feasibility of encapsulating the most widely used precursor in clinical nuclear diagnostic imaging, the γ-emitting [^99mTc]­TcO₄^– anion, under conditions compatible with in vivo administration. Subsequent single-photon emission computed tomography imaging of the caged-anion reveals a marked change in the biodistribution compared to the thyroid-accumulating free oxo-anion, thus moving clinical applications of (metallo)­supramolecular species a step closer.