先前我们证实正常脑组织高表达的circ-SHPRH及其编码蛋白SHPRH-146aa在人脑胶质母细胞瘤表达下降，上调人脑胶质瘤细胞株U251 和 U373 circ-SHPRH表达抑制肿瘤增殖，进而发现其可能与细胞自噬相关，后者的作用强弱和时效尚待深入研究。早先我们以细胞凋亡自噬的标志物磷脂酰乙醇胺(PE)为靶标，自行研制出小分子多肽18F-AlF-NOTA-PEG3-Dur显像剂，体外细胞结合实验证实细胞摄取良好、体内生物分布实验符合预期，正常小动物和胶质瘤荷瘤鼠PET显像均初步证实可特异性与凋亡细胞结合。结合上述基础，进一步建立人脑胶质瘤颅内和皮下荷瘤鼠动物模型，circ-SHPRH基因靶向治疗后，采用18F-AlF-NOTA-PEG3-Dur显像监测，实时进行人脑胶质瘤靶向诱导肿瘤细胞死亡活体动态分子显像，确立circ-SHPRH基因作用强度和时效，实现早期、无创、动态监测肿瘤治疗。

Circ-SHPRH is a circRNA. It has been found by our team that the protein SHPRH-146aa encoded by circ-SHPRH are abundantly expressed in normal human brains and are down-regulated in glioblastoma. The overexpression of SHPRH-146aa in U251 and U373 glioblastoma cells reduces their malignant behavior and tumorigenicity. Advanced research of our lab preliminarily reveals conversion of the key protein LC3B and upgrade of SQSTM1, the biomarker of cell autophagy, suggesting that SHPRH-146aa potentiates glioma cell autophagy. But it is necessary to intensively study the dynamic tumor changes and duration of its effects in vivo. Phosphatidylethanolamine (PE) transfering from inner layer to outer layer of cell membrane during programmed cell death, is the biomarker of apoptosis and autophagy. Targeting PE, our group has developed a new molecular imaging agent called 18F-AlF-NOTA-PEG3-Dur with satisfactory cell absorption in vitro and expectant distribution in vivo. PET scan of both the normal mice and the glioblastoma xenograft nude mice confirmed its specific binding to apoptotic cells. Based on the above fundamental research, after the establishment of xenograft brain tumor formation in nude mice intracranially and subcutaneously with treatment of circSHPRH target therapy, we could use 18F-AlF-NOTA-PEG3-Dur imaging to track the dynamic molecular image of induced tumor cell death and to ascertain the effect and duration of circSHPRH. Early stage, non-invasive and dynamic clinical evidences can be obtained promisingly.