18F-A1F-NOTA-c（CGRRAGGSC）的制备和生物学评价

Synthesis and biological evaluation of 18F-AIF-NOTA-c （CGRRAGGSC）

目的制备18F-A1F-1，4，7-三氮环壬烷-1，4，7-三乙酸（NOTA）-C（CGRRAGGSC），并研究其对白细胞介素（IL）-11受体（IL-11R）阳性肿瘤的靶向性。方法将c（CGRRAGGSC）偶联NOTA后采用A1F法进行标记。高效液相色谱（HPLC）测定18F-AIF-NOTA-c（CGRRAGGSC）的放化纯及稳定性。建立SKOV3荷瘤裸鼠模型，静脉注射18F-A1F-NOTA-c（CGRRAGGSC）后30min、1h、2h行microPET显像，测定主要脏器的放射性摄取值。采用DAS2．0软件计算药代动力学参数。结果18F-A1F-NOTA-c（CGRRAGGSC）的产率为（30．0±7．4）％，放化纯大于95％，磷酸盐缓冲液和血浆中至少稳定2h。MicroPET图像上可见该标记物在肿瘤部位的浓聚。注射后30min、1h、2h，肿瘤／肌肉摄取比值分别为6．26±2．98、7．19±3．63、9．05±4．30。标记物进入血液后快速清除并通过肝脏和肾脏代谢，其分布半衰期为（0．38±0．14）h，消除半衰期为（2．64±0．28）h。结论18F-A1F-NOTA-c（CGRRAGGSC）制备过程简单，标记条件温和，产物与受体有较好的结合特性，是一种潜在的IL-11R阳性肿瘤靶向显像剂。

Objective To synthesize 18F-AIF-1,4,7-triazacyclononane-l,4,7-triacetic acid （NOTA）- c （CGRRAGGSC）, which could specifically bind to the α chain of interleukin （IL）- 11 receptor （IL-11R）, and evaluate its targeting potential to IL-11 R-positive tumors. Methods Polypeptide c （CGRRAGGSC） was first coupled with NOTA and then labeled with 18F by A1F labeling method. The radioehemical purity and ra- dioehemical yield of 18F-AIF-NOTA-c（CGRRAGGSC） were analyzed by high performance liquid chromatog- raphy, and the stability in vitro was evaluated. The tracer biodistribution in tumor-bearing mice （cell line SKOV3） was evaluated by the dynamic imaging with microPET 30 min, 1 h, 2 h after injection of 18F-A1F- NOTA-c （ CGRRAGGSC ）. The tracer kinetics was performed in normal mice. Pharmacokinetics parameters were calculated using DAS2.0 software. Resdts The radiochemical purity of 18F-A1F-NOTA-c （CGRRAGGSC） was higher than 95% and the radiochemieal yield was （30.0±7.4）%. It could be stably maintained in phosphate- buffered solution and plasma for at least 2 h. MieroPET imaging showed that 18F-A1F-NOTA-c （CGRRAGGSC） had a good affinity to SKOV3 tumor. The tumor/muscle ratios at 30 min, 1 h, 2 h after the injection of 18F- A1F-NOTA-c（CGRRAGGSC） were 6.26±2.98, 7.19±3.63 and 9.05±4.30, respectively. The tracer was cleared rapidly in blood and mainly excreted by the liver and kidneys. The Tw, and T1/2~ were （0.38±0.14） h and （2.64±0.28） h, respectively. Conclusions ts F-A1F-NOTA-e （CGRRAGGSC） is easy to be synthe- sized and has a good affinity to IL-11 R-positive tumors. It will be a potential IL-11 R-targeting imaging agent.