肿瘤放疗耐受早期预警及精确监测的半乳糖凝集素-1靶向PET分子显像

放疗是目前临床上最常用的肿瘤治疗手段之一。然而，由于肿瘤组织生产过快、耗氧量增加以及血管异常造成的乏氧严重影响着放疗的有效性。针对目前肿瘤乏氧显像剂如18F-FMISO低乏氧显像特异性等缺点，本项目拟设计构建基于肿瘤微环境半乳糖凝集素-1的多肽PET显像探针。在高转移小鼠乳腺癌模型中，研究制备的PET显像探针的乏氧显像特异性，以及如何通过小动物分子影像学研究为肿瘤乏氧提供精确的分子信息，从而早期精准预警放疗耐受。同时，针对半乳糖凝集素-1设计构建纳米载药体系，通过小动物PET显像监测其在逆转肿瘤放疗耐受中的作用，并通过PET显像指导其与放疗的合理联合治疗，以达到最佳的肿瘤治疗效果。

Radiotherapy is currently one of the most commonly used strategies for tumor therapy. However, resistance to radiotherapy is a pervasive problem in clinical oncology; one of the chief causes of radiotherapy resistance is tumor hypoxia. The hypoxia imaging agents frequently used in current practice, such as 18F-FMISO, produce low tumor-to-background ratios, and exhibit low sensitivity and nonspecificity. In this proposal, we propose to design and synthesize a new peptide based PET imaging probe by specific targeting of galectin-1. The hypoxia specificity of this probe will be evaluated and characterized in a highly metastatic breast cancer mouse model. We will investigate whether galectin-1 targeted PET imaging of hypoxia could predict early tumor resistance to radiotherapy. Moreover, a nano-delivery system for galectin-1 specific inhibition will also be developed for reversing radiotherapy resistance. Towards effective tumor eradication, rational design of a combination of galectin-1 inhibition and radiotherapy will be performed under the guidance of PET imaging.