基于PCM-Fe3O4/PFP多模态分子成像早期评价阿霉素心肌损伤的实验研究

阿霉素是一线临床化疗药物，广泛地用于各系统恶性肿瘤的治疗，但其心脏毒性发生率高，预后差。如何无创早期发现及准确评估阿霉素心肌损伤对指导临床治疗和改善患者预后尤为重要，但目前尚缺乏针对心肌损伤的早期、敏感及无创监测手段。结合我们的前期研究基础及文献报道，本研究首先建立中华小型猪阿霉素心肌损伤模型，应用CMR多参数评估阿霉素引起不同阶段心肌组织学表征和病理变化，探寻心肌早期损伤的影像学标志物和最佳治疗时间窗，阻止心肌发生不可逆损伤；拟构建PCM-Fe3O4/PFP探针体系，在磁共振及超声无创监测下快捷及安全清除阿霉素引起心肌损伤时产生的过量活性氧的新策略，从而抑制或预防阿霉素化疗引起的心肌损伤，降低心脏毒性，探究并阐释其相关氧化应激机制。相关研究成果可望为早期监测蒽环类药物心肌损伤、积极探索干预措施及及全程动态评价治疗效果提供新的影像学平台，也为临床化疗后预防心肌损伤药物研发提供了新的视角。

Adriamycin is a clinical first-line chemotherapy drugs, widely used in the treatment of various malignant tumors, but the incidence of cardiotoxicity is high and the prognosis is poor. How to discover without harm in the early stage and evaluate precisely adriamycine-induced myocardial injury is particularly important for guiding clinical treatment and improving the prognosis. However, there is still lack of early, sensitive and noninvasive monitoring methods for myocardial injury. Based on our previous research foundation and literature reports, Chinese mini-swine adriamycine-induced myocardial injury model was established firstly. Using multi-parameters CMR evaluate the myocardial histological characterization and pathological changes caused by adriamycin at different stages, so explore early myocardial injury imaging markers and determine the most optional treatment time window for preventing irreversible damage to the myocardium.To build a PCM-Fe3O4/PFP probe system monitor scavenger of reactive oxygen species (ROS) quickly and safely during adriamycin-induced myocardial injury by using magnetic resonance and ultrasound and would thus inhibit or prevent anthracycline -induced myocardial injury, diminish cardiotoxicity, investigate and explain related oxidative stress mechanism. Related research achievements are likely to monitor myocardial injury induced by anthracyclines, to explore interventions actively, and to provide a new imaging platform for the whole dynamic evaluation of the treatment effect, as well as to bring us new perspectives for drug research and development that could prevent myocardial injury after chemotherapy. This has good applied prospect in clinical practice.