基于细胞凋亡的MR/PET分子影像对非小细胞肺癌疗效评估的研究

Response evaluation criteria for solid tumors (RECIST) are currently used to assess the response of non-small cell lung cancer (NSCLC); however, it depends on morphological measurements, resulting in delayed evaluation or underestimation of therapeutic effects. Apoptosis is an early molecular event following radio-chemotherapy and is regarded as an effective biomarker for treatment efficiency evaluation. In preliminary studies, we developed 18F-Annexin V PET probe to image apoptosis in lung cancer, but it is difficult to depict other molecular features of NSCLC. Multimodality molecular imaging, such as MR/PET combining high spatial resolution and multiparameter imaging ability of MR and high sensitivity of PET to detect molecular events has a major advantage in the noninvasive detection of apoptosis and simultaneous decection of other molecular events. This project will develop 18F-Annexin V MR/PET apoptosis probe and validate its specific apoptosis imaging efficiency through comparing with 18F-FDG PET, diffusion weighted imaging, and investigate its value in evaluating early therapy effects in NSCLC. It is anticipated that 18F-Annexin V MR/PET apoptosis imaging is a sensitive biomarker for evaluating early therapy effects following chemotheraphy of NSCLC. This new MR/PET apoptosis imaging can provide a new molecular imaging method for real time, noninvasive evaluation of NSCLC therapy effects, and present scientific evidence for real time adjustment of personalized treatment plan for patients with NSCLC.

临床上采用实体肿瘤疗效评价标准（RECIST）评估非小细胞肺癌（NSCLC）放化疗疗效，但仅根据形态变化导致评估滞后或低估疗效。凋亡是肿瘤放化疗后出现的早期分子事件，是NSCLC放化疗后早期疗效评估的理想标志。前期研究显示18F-Annexin Ⅴ PET可用于肺癌凋亡显像，但难以全面刻画NSCLC的分子特征。MR/PET结合MR的高空间分辨率、多参数成像能力和PET的高敏感性，能多维无创检测肿瘤细胞凋亡并同步描绘其他分子事件。本研究拟研发18F-Annexin Ⅴ MR/PET凋亡分子探针，在体外细胞和活体动物水平验证其凋亡特异成像效能并与18F-FDG PET、扩散加权成像等MR技术比较，研究其在NSCLC疗效评估中的价值。预期MR/PET凋亡成像可作为NSCLC放化疗后早期疗效评估高敏感的影像表征，最终为临床提供一种实时无创评估NSCLC疗效的新方法，为治疗方案实时调整提供科学依据。

临床上采用实体肿瘤疗效评价标准（RECIST）评估非小细胞肺癌（NSCLC）放化疗疗效，但仅根据形态变化导致评估滞后或低估疗效，因此需要探讨一种早期无创评估NSCLC疗效的新方法。凋亡是肿瘤放化疗后出现的早期分子事件，是NSCLC放化疗后早期疗效评估的理想标志。本研究制备了基于纳米颗粒的探针Au star-PB，探讨了其多模态成像能力；制备了细胞凋亡探针125I-Annexin V、18F-ML-10，探讨了其在NSCLC疗效评估中的价值。结果显示Au star-PB纳米探针具有CT/MRI/光声三模态成像的能力，18F-ML-10 microPET显像能显示化疗后早期的细胞凋亡。因此多功能Au star-PB的成功制备为多模态成像探针的制备奠定了坚实基础，凋亡分子显像为NSCLC放化疗后早期疗效评估提供了一种新方法。