Lv Peng-Cheng, Putt Karson S, Low Philip S
Institute for Drug Discovery and ‡Department of Chemistry, Purdue University , West Lafayette, Indiana 47907 United States.
Bioconjug Chem. 2016 Jul 20;27(7):1762-9. doi: 10.1021/acs.bioconjchem.6b00271. Epub 2016 Jul 7.
As tumors grow, vasculature is often deficient or malformed, resulting in many localized areas of hypoxia. Cells located in these hypoxic regions exhibit an altered gene expression pattern that can significantly alter resistance to conventional anticancer treatments such as ionizing radiation and chemotherapeutic drugs. A priori knowledge of the level of hypoxia within a tumor may better guide clinical care. In an effort to create a hypoxia specific imaging agent, a ligand for the tissue hypoxia marker, carbonic anhydrase IX (CA IX), was synthesized and used as a targeting ligand to deliver an attached (99m)Tc-chelating agent. Binding of the resulting conjugates to hypoxic cancer cells was first characterized in vitro. Whole animal imaging and biodistribution studies then were performed to determine tumor specificity in vivo. Several conjugates were found to bind selectively to CA IX expressing tumors in a receptor-dependent manner. We suggest that such conjugates could prove useful in identifying hypoxic cancers and/or quantitating the level of hypoxia within a tumor.
随着肿瘤的生长，血管系统常常不足或畸形，导致许多局部缺氧区域。位于这些缺氧区域的细胞表现出改变的基因表达模式，这可显著改变对传统抗癌治疗如电离辐射和化疗药物的抗性。肿瘤内缺氧水平的先验知识可能更好地指导临床护理。为了创建一种缺氧特异性成像剂，合成了一种针对组织缺氧标志物碳酸酐酶IX（CA IX）的配体，并用作靶向配体以递送附着的（99m）Tc螯合剂。首先在体外表征所得缀合物与缺氧癌细胞的结合。然后进行全动物成像和生物分布研究以确定体内肿瘤特异性。发现几种缀合物以受体依赖性方式选择性地结合表达CA IX的肿瘤。我们认为，此类缀合物可能在识别缺氧癌症和/或定量肿瘤内的缺氧水平方面证明是有用的。
