耐久霉素[18F]FPDuramycin-PET凋亡显像对软组织肉瘤冷冻消融精准功能影像评估的分子机制

软组织肉瘤（STS）是一类高度恶性的肿瘤，术后复发率80%以上，传统治疗难以获得满意疗效。我们前期采用氩氦刀冷冻消融治疗STS，取得显著成效，但发现消融坏死区周边的肿瘤细胞常因免疫凋亡不全而复发，而常规CT、MR及PET难以准确区分凋亡与肿瘤残余组织，直接影响治疗方案的选择与疗效提高；同期合成的[18F]标记耐久霉素靶向磷脂酰乙醇胺的凋亡显像剂（[18F]FPDuramycin），可高效检测裸鼠肿瘤化疗后细胞凋亡的区域，但是否有望用于冷冻消融的疗效评估尚待证实。鉴此，本项目将[18F]FPDuramycin运用于兔VX2肉瘤模型中：1.证实其在体显像的安全性、分布及量效关系；2.明确其显示消融范围的敏感性及特异性；3.阐明其评估冷冻消融疗效的显像分子机制。本研究预期将揭示[18F]FPDuramycin-PET凋亡显像的分子机制，为确立一种新的肿瘤消融疗效的功能影像评价方法提供科学依据。

Soft tissue sarcoma (STS) is a kind of highly malignant tumor with more than 80% recurrent rate and poor quality of life in patients. Argon-helium cryoablation has been used to treat STS in our previous study. Although remarkable effect was confirmed, we found that some tumor cells in the relative necrotic area might develop to be residual recurrence because of incomplete apoptosis by autoimmunity. These relative necrotic cells were difficult to be identified accurately by conventional CT, MR and FDG-positron emission tomography (PET). One novel apoptosis imaging agent for PET imaging tracer [18F]F labeled Duramycin named [18F]FPDuramycin has been synthesized previously. It has presented highly biological safety and efficiently detected the area of cell apoptosis nude in mice tumor after chemotherapy. It is expected to be an effective imaging agent to confirm the ablation range accurately. Therefore, this study proposes to use [18F]FPDuramycin in rabbit VX2 subcutaneous transplantation tumor model to confirm the safety, distribution and dose-effect relationship. Then the sensitivity and specificity would be analyzed. Finally, its imaging mechanism is planned to investigate. In this study, we are expecting to reveal the molecular mechanism of [18F]FPDuramycin-PET in apoptosis imaging and provided the scientific basis in developing a new functional imaging method for evaluation of the tumor cryoablation efficacy.