^(18)F-黄连素衍生物:一种潜在的PET/CT肿瘤靶向分子显像剂

^(18)F-Berberine Derivatives:a Potential Molecular Imaging Agent for Tumor Targeting by PET/CT Tumor

癌症是导致人类死亡的主要原因之一,肿瘤学医师对肿瘤的诊断、分期、监测治疗反应及随访等越来越依赖于医学影像技术。如今,18F-脱氧葡萄糖(18F-FDG)PET/CT在临床肿瘤患者的管理中发挥着重要作用。然而,18F-FDG并非肿瘤特异性显像剂,炎症和感染性疾病也可高度浓集18 F-FDG,导致假阳性;有些肿瘤摄取18 F-FDG低甚至不摄取,导致假阴性。开发非18F-FDG新型靶向肿瘤显像剂是我们面临的一项紧迫任务。近年来,大量体外研究证明,黄连素通过抑制肿瘤细胞线粒体呼吸链等,诱导细胞凋亡,具有抗多种肿瘤细胞活性。但一直缺乏黄连素在生物活体内具有靶向性分布的证据。我们提出并用18 F-黄连素衍生物PET/CT荷VX2肌肉肿瘤兔模型显像方法验证"黄连素在生物活体内具有肿瘤靶向性分布"的假说。本综述将简要概述黄连素抗癌研究的进展、黄连素抗癌作用的结构基础以及迄今已确定的黄连素抗癌作用的分子机制,介绍18F-黄连素衍生物PET/CT荷VX2肌肉肿瘤兔模型显像,首次实现活体生物体内肿瘤的"可视化"。这些突破性的研究结果表明,18 F-黄连素衍生物作为一种潜在的PET/CT肿瘤靶向分子显像剂,对癌症的靶向治疗、分子显像及中药现代化具有重要意义。

Cancer is one of the main causes of death for human beings.Clinical oncologists increasingly rely upon imaging for diagnosis,stage,response assessment,and follow-up in cancer patient.However,18F-FDG is not a tumor specific agent,inflammation and infection also have intensive uptake of ^18F-FDG,resulting in false positive diagnosis,and some tumors have low uptake of ^18F-FDG or even do not uptake 18F-FDG,leading to false negative diagnosis.So it is urgent to develop non-^18F-FDG novel tumor targeting agent.Recently,a large number of researches in vitro have demonstrated that berberine has anti-tumor activity against a variety of tumor cells by inducing tumor cell apoptosis through inhibition of mitochondrial respiratory chain etc.So far,there is no credible evidence of berberine targeting in tumor in vivo.We proposed a hypothesis that berberine has the characteristics of tumor targeting biodistribution in vivo,and verified the proposal by ^18F-berberine PET/CT imaging in VX2 muscle tumor-bearing rabbit model.In this review,we intend to give an overview of the progress of berberine anticancer,the structural bases of berberine anticancer and the uderlying molecular mechanisms of berberine anticancer indentified so far.We also introduce the first visualization of ^18F labeled berberine derivatives targeting tumor in VX2 muscle tumor-bearing rabbit model by PET/CT.These breakthrough findings suggest that 18F-berberine derivatives as a potential PET/CT tumor targeted molecular imaging agent may have important implications for cancer targeting therapy,molecular imaging and modernization of Traditional Chinese Medicine.