Burke Benjamin P, Grantham William, Burke Michael J, Nichol Gary S, Roberts David, Renard Isaline, Hargreaves Rebecca, Cawthorne Christopher, Archibald Stephen J, Lusby Paul J
Department of Chemistry , University of Hull , Cottingham Road , Hull HU6 7RX , United Kingdom.
Positron Emission Tomography Research Centre , University of Hull , Cottingham Road , Hull HU6 7RX , United Kingdom.
J Am Chem Soc. 2018 Dec 12;140(49):16877-16881. doi: 10.1021/jacs.8b09582. Epub 2018 Dec 3.
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 CoL tetrahedron we now show the feasibility of encapsulating the most widely used precursor in clinical nuclear diagnostic imaging, the γ-emitting [Tc]TcO 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.
非共价封装是一种用于改变治疗和诊断物质的功效及物理化学性质的有吸引力的方法。非生物自组装结构已显示出前景，但在体外研究和（临床前）临床研究之间仍存在许多障碍，尤其是在非平衡条件下维持大分子空心结构所面临的挑战。我们现在利用动力学稳定的CoL四面体表明，在与体内给药兼容的条件下，封装临床核诊断成像中最广泛使用的前体——发射γ射线的[Tc]TcO阴离子是可行的。随后对笼形阴离子进行的单光子发射计算机断层扫描成像显示，与甲状腺蓄积的游离氧阴离子相比，生物分布有显著变化，从而使（金属）超分子物质的临床应用又向前迈进了一步。
