Department of Chemistry, McMaster University, Hamilton, Ontario L8S 4M1, Canada.
J Am Chem Soc. 2009 Mar 4;131(8):2906-16. doi: 10.1021/ja8078175.
A series of aliphatic polyester dendrons, generations 1 through 8, were prepared with a core p-toluenesulfonyl ethyl (TSe) ester as an easily removable protecting group that can be efficiently replaced with a variety of nucleophiles. Using amidation chemistry, a tridentate bis(pyridyl)amine ligand which is known to form stable complexes with both Tc(I) and Re(I) was introduced at the dendrimer core. Metalation of the core ligand with (99m)Tc was accomplished for generations 5 through 7, and resulted in regioselective radiolabeling of the dendrimers. The distribution of the radiolabeled dendrimers was evaluated in healthy adult Copenhagen rats using dynamic small-animal single photon emission computed tomography (SPECT). The labeled dendrimers were cleanly and rapidly eliminated from the bloodstream via the kidneys with negligible nonspecific binding to organs or tissues being observed. These data were corroborated by a quantitative biodistribution study on the generation 7 dendrimer following necropsy. The quantitative biodistribution results were in excellent agreement with the data obtained from the dynamic SPECT images.
一系列脂肪族聚酯树枝状分子，1 代到 8 代，均以易于去除的对甲苯磺酰基乙酯（TSe）酯作为核心保护基团来制备，该保护基团可被多种亲核试剂高效取代。采用酰胺化化学方法，在树枝状分子核心处引入了一种三齿双（吡啶基）胺配体，已知该配体可与 Tc（I）和 Re（I）形成稳定的配合物。用（99m）Tc 对核心配体进行金属化，可实现 5 代到 7 代的树枝状分子的区域选择性放射性标记。通过动态小动物单光子发射计算机断层扫描（SPECT）评估健康成年哥本哈根大鼠中放射性标记树枝状分子的分布。标记的树枝状分子通过肾脏迅速且干净地从血液中清除，几乎没有观察到器官或组织的非特异性结合。这些数据通过对 7 代树枝状分子的定量生物分布研究在解剖后得到了证实。定量生物分布结果与来自动态 SPECT 图像的数据非常吻合。
