基于上海同步辐射光源同轴相衬成像双模双靶向肺癌早期诊断研究

Lung cancer is the leading cancer in morbidity and mortality currently. However, it is difficult for early detection of the cancer. Computerized tomography (CT) is very often used for diagnosis of the disease clinically, which based on the difference of X- ray absorption between the malignant tissues and the normal tissues. However, the difference in absorption is marginal on the early stage of lung cancer, leading to low detection sensitivity and specificity. Synchrotron radiation in-line phase contrast imaging has high soft tissue contrast and detection sensitivity, and is suitable for early detection of lung cancer. In current study, we will explore early detection of lung cancer with in-line phase contrast imaging based on Shanghai Synchrotron Radiation Facility (SSRF). In addition, tumor angiogenesis is mainly distributed in the periphery of tumor. We hypothesize that specific probes made with high density materials (e.g. Au) for tumor angiogenesis would not only enhance the detection sensitivity but also demarcate the tumor and the normal tissue. Moreover, EGFR is upregulated on non-small lung cancer. Therefore, the specific probes targeting tumor angiogenesis and tumor cells will also be synthesized facilitating early and specific detection of the cancer. In this study, we mainly focus on: (1) phase contrast iconography of lung cancer; (2) preparation of Au nano probes specific tumor angiogenesis and its distribution in vivo; (3) early detection of lung cancer with in suit tumor model. We hope a new paradigm for early detection of lung cancer would be established by our study.

肺癌发病率、致死率均居恶性肿瘤之首。CT是目前肺癌诊断首选方法,其依据不同组织对X射线的吸收差异进行成像。但对早期肺癌，癌变和正常组织对X射线吸收差异性小，CT难以实现早期、特异诊断。同步辐射X射线具有高空间相干性，可进行相衬成像。相比于吸收成像，相衬成像具有非常高的软组织分辨率和灵敏性（>1000倍），适合肺部疾病的探测。本项目拟基于上海同步辐射X射线同轴相衬成像装置，在制备非小细胞肺癌新生血管αvβ3受体和肿瘤细胞EGFR受体双受体靶向、具有相衬和SPECT双模态成像功能金纳米棒探针的基础上，探索肺癌早期、特异诊断的新模式。双模、双受体靶向探针既可强化肿瘤组织与正常组织边界（新生血管靶向）衬度，又能强化肿瘤实质（细胞靶向）衬度，在实现肿瘤边界界定的同时，也进一步降低了肿瘤的探测限，真正实现肺癌早期、特异的诊断！其成功将为发展同步辐射X射线相衬成像肺癌早期诊断方法提供经验和借鉴。

肺癌发病率、致死率均居恶性肿瘤之首。CT是目前肺癌诊断首选方法，其依据不同组织对X 射线的吸收差异进行成像。但对早期肺癌，癌变和正常组织对X射线吸收差异性小，CT难以实 现早期、特异诊断。同步辐射X射线具有高空间相干性，可进行相衬成像。相比于吸收成像， 相衬成像具有非常高的软组织分辨率和灵敏性（>1000倍），适合肺部疾病的探测。本项目基于上海同步辐射X射线同轴相衬成像装置(BL13W线站)，以金纳米棒为基础，制备具有非小细胞肺癌新生血管αvβ3受体和肿瘤 细胞EGFR受体双受体靶向、同时标记有放射性核素碘-125，具有相衬和SPECT双模态成像功能金纳米棒探针。同单一靶向探针，双受体靶向探针体内既可强化肿瘤组织与正常组织边界（新生 血管靶向）衬度，又能强化肿瘤实质（细胞靶向）衬度，在实现肿瘤边界界定的同时，也进一 步降低了肿瘤的探测限，肿瘤尺寸在5毫米左右可实现探测，达到了肺癌早期、特异的诊断的要求！我们的研究表明：同步辐射相衬成像复合分子影像探针技术能够实现肺 癌早期、特异诊断，也为发展同步辐射X射线相 衬成像肺癌早期诊断方法提供经验和借鉴。