碳酸酐酶Ⅸ在核医学中的研究进展

摘要

Carbonic anhydrase K (CA IX), which is one of carbonic anhydrases (Cas), is a tumor-associated transmembrane protein. CA IX is detected in various solid tumors, but little or not in the normal tissues; it catalyzes a reversible conversion of carbon dioxide to bicarbonate and proton, controlling Ph of intracellular and extracellular space and maintaining the acid-base balance of tissues in favor of tumor growth and invasion. CA IX is clearly an attractive target for anti-tumor drugs and also as a prognostic factor of patients in the diagnosis and treatment of tumors. CA IX inhibitors can be used as diagnostic drugs for molecular imaging of tumors and also be used as anti-tumor drugs for blocking the CA IX mediated pathway. Molecular imaging using 89Zr, 111In. 124I or 125I labeled monoclonal antibodies targeting CA IXX can precisely position the distribution and sensitively detect expression of CA IX. In radioimmunotherapy experiments at maximum tolerated dose, tumor growth was effectively delayed by monoclonal antibodies targeting CA IX labeled with 90 Y, 131I, 177Lu or 186 Re. This review focused on the presentation of CA IX and its applications in the nuclear medicine research.%碳酸酐酶Ⅸ(Carbonic anhydrase Ⅸ,CA Ⅸ)是碳酸酐酶家族(Carbonic anhydrases,CAs)的异构体之一,在许多肿瘤中过量表达,是一种与肿瘤相关的跨膜糖蛋白.它催化CO2水解为碳酸氢根和氧离子,维持肿瘤细胞内的pH,酸化细胞外环境,有利于肿瘤的生长和转移.在核医学的靶向诊断和治疗中,CA Ⅸ成为一个抗肿瘤药物的靶向目标,也成为病人病情的一个预后因子.CAⅨ抑制剂可以作为一种诊断药物,用于肿瘤的分子影像；也可以作为一种治疗药物,阻断CAⅨ所调控的通路.利用89Zr、111In、124I或125I标记靶向CA Ⅸ的单克隆抗体或其片段进行分子影像,能精确定位CA Ⅸ的分布,灵敏检测CA Ⅸ的表达情况；利用90Y、131I、127Lu或186Re标记靶向CA Ⅸ的单克隆抗体,在放免疫治疗中可有效延迟肿瘤的生长.本文对CA Ⅸ及其在核医学中的研究进展进行了综述.