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目的:制备一种n 68Ga标记的人表皮生长因子受体2(HER2)亲和体显像剂n 68Ga-1，4，7-三氮环壬烷-1，4，7-三乙酸(NOTA)-马来酰亚胺(MAL)-半胱氨酸(Cys)-甘氨酸-甘氨酸-甘氨酸-精氨酸-天冬氨酸-天冬酰胺-HERn 2：342亲和体(GGGRDN-ZHERn 2：342) (简称n 68Ga-MZHER)，探讨其microPET显像及生物分布。n 方法:采用“一步法”对多肽NOTA-MAL-Cys-GGGRDN-ZHERn 2：342进行n 68Ga标记，得到n 68Ga-MZHER，测定其标记率、放化纯及体外稳定性。取ICR小鼠24只，注射n 68Ga-MZHER 1.85 MBq，并于注射后15、30、60和120 min分别处死(每时间点6只)，获得主要器官的放射性计数，计算每克组织百分注射剂量率(%ID/g)。行microPET动态观察n 68Ga-MZHER在正常小鼠体内的生物分布。建立HER2阳性的卵巢癌SKOV-3荷瘤裸鼠模型8只，于n 68Ga-MZHER注射后30、60和120 min时分别进行静态显像；预先按体质量10 mg/kg注射未标记Cys-ZHERn 2：342后30 min，再注入n 68Ga-MZHER，60 min后采集图像。勾画感兴趣区(ROI)，获得时间-放射性曲线(TAC)。另取正常小鼠6只进行安全性研究。n 结果:68Ga-MZHER合成时间约15 min，标记率>90%，放化纯>95%，室温放置120 min放化纯仍>95%。ICR小鼠生物分布示n 68Ga-MZHER主要经肾排泄，在其他组织中清除较快；注射后15 min肾摄取为(106.36±15.74) %ID/g，且随着时间延长逐渐升高，最高达(145.15±28.04) %ID/g (60 min)，120 min后降至(86.12±22.75) %ID/g。探针在小鼠体内血液药代动力学分布符合二室模型。荷瘤裸鼠microPET显像示SKOV-3移植瘤清晰可见，与本底对比度良好。注射n 68Ga-MZHER后30、60和120 min，SKOV-3移植瘤的摄取分别为(11.26±0.50)、(12.27±1.13)和(12.65±0.89) %ID/g；注射后60 min，阻断后的SKOV-3移植瘤对探针的摄取为(1.25±0.28) %ID/g。安全性研究表明，小鼠注射n 68Ga-MZHER后30 d，健康存活，病理学检查主要器官未见明显异常。n 结论:68Ga-MZHER制备方便、体外稳定性好、药代动力学性能良好、显像性能优良且安全，这有助于探针的后续开发及临床应用研究。n “,”Objective:To prepare a n 68Ga labeled human epidermal growth factor receptor 2 (HER2) affibody n 68Ga-1, 4, 7-triazacylononane-1, 4, 7-triacetic acid (NOTA)-maleimide (MAL)-Cysteine (Cys)-Glycine-Glycine-Glycine-Arginine-Aspartic acid-asparagine-HERn 2: 342 affibody (GGGRDN-ZHERn 2: 342)(n 68Ga-MZHER), and evaluate its biodistribution and microPET characteristics.n Methods:NOTA-MAL-Cys-GGGRDN-ZHERn 2: 342 conjugate was labeled with n 68Ga in one step. Radiochemical purity, radiolabeling yield and stability n in vitro were analyzed. Normal mice (n n=24) were scarified at 15, 30, 60 and 120 min postinjection (1.85 MBq n 68Ga-MZHER) to measure radioactive counts (percentage activity of injection dose per gram of tissue (%ID/g)) in main organs. Biodistribution and kinetics were evaluated by dynamic microPET in mice. Ovarian cancer (SKOV-3) models were established and microPET was performed at 30, 60 and 120 min postinjection of radiotracer. After administration of unlabeled Cys-ZHERn 2: 342 peptide (10 mg/kg body weight) for 30 min, n 68Ga-MZHER was injected into mice and PET images were acquired at 60 min postinjection. Region of interest (ROI) was drawn to access time-activity curve (TAC) in main organs and tumor. Six normal mice were used for the safety study.n Results:68Ga-MZHER was synthesized in about 15 min with the yields more than 90%, and radiochemical purity more than 95%. The radiochemical purity was also determined to be more than 95% after being stored for 120 min at room temperature. Predominant uptake of n 68Ga-MZHER was in the kidneys, and was cleared rapidly in normal tissues except the kidney. At 15 min postinjection, the renal uptake value was (106.36±15.74) %ID/g, then gradually increased with time, up to (145.15±28.04) %ID/g (60 min), and decreased to (86.12±22.75) %ID/g after 120 min postinjection. The blood pharmacokinetic of the probe in mice was fit with the two-compartment model. MicroPET imaging in mice bearing HER2 positive SKOV-3 tumors showed that the xenografts were clearly visualized with good contrast to normal tissue. The uptakes in tumors was determined to be (11.26±0.50), (12.27±1.13) and (12.65±0.89) %ID/g at 30, 60 and 120 min postinjection. Block experiment showed that the corresponding values decreased to (1.25±0.28) %ID/g at 60 min postinjection. Safety studies showed that after injection of n 68Ga-MZHER for 30 d, the mice survived and no obvious abnormalities were observed in the main organs as shown in pathological results.n Conclusions:68Ga-MZHER can be successfully labeled by one-step method. The n 68Ga-MZHER probe owns the advantages of favorable imaging properties, convenient preparation, excellent stability, safety, rapid clearance in the blood, which support its application for further research.n