[1]王 伟,林建国,刘桂青,等.新型肿瘤凋亡显像PET探针的制备与表征[J].南京理工大学学报(自然科学版),2018,42(01):107.[doi:10.14177/j.cnki.32-1397n.2018.42.01.016]
 Wang Wei,Lin Jianguo,Liu Guiqing,et al.Preparation and characterization of novel PET molecularprobe for detecting tumor apoptosis[J].Journal of Nanjing University of Science and Technology,2018,42(01):107.[doi:10.14177/j.cnki.32-1397n.2018.42.01.016]
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新型肿瘤凋亡显像PET探针的制备与表征()
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《南京理工大学学报》(自然科学版)[ISSN:1005-9830/CN:32-1397/N]

卷:
42卷
期数:
2018年01期
页码:
107
栏目:
出版日期:
2018-02-28

文章信息/Info

Title:
Preparation and characterization of novel PET molecular probe for detecting tumor apoptosis
文章编号:
1005-9830(2018)01-0107-07
作者:
王 伟12林建国2刘桂青12邱 玲12吕高超2李 珂2罗世能12
1.江南大学 化学与材料工程学院,江苏 无锡 214122; 2.江苏省原子医学研究所, 卫生部核医学重点实验室,江苏省分子核医学重点实验室,江苏 无锡 214063
Author(s):
Wang Wei12Lin Jianguo2Liu Guiqing12Qiu Ling12 Lv Gaochao2Li Ke2Luo Shineng12
1.School of Chemical and Materials Engineering,Jiangnan University,Wuxi 214122,China; 2.Key Laboratory of Nuclear Medicine,Ministry of Health and Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi 214063,China
关键词:
正电子发射断层显像 凋亡显像探针 肿瘤凋亡 分子探针 多肽DEVD 一步18F标记 点击化学
Keywords:
positron emission tomagraphy apoptosis imaging probe tumor apoptosis molecular probe peptide DEVD one-step 18F-radiolabeling click chemistry
分类号:
O06
DOI:
10.14177/j.cnki.32-1397n.2018.42.01.016
摘要:
设计合成一种可检测肿瘤凋亡的新型正电子发射断层显像(PET)探针,并对其理化性质和生物学性质进行研究。采用“点击化学”反应将标记基团和含天门冬氨酸-谷氨酸-缬氨酸-天门冬氨酸(Asp-Glu-Val-Asp,DEVD)序列的多肽连接得到标记前体1,通过简便的一步18F标记方法制得放射性分子探针18F-1,分别考察了它在PBS缓冲液和血清中的稳定性,并对其脂水分配系数进行了检测。结果显示,制备18F-1所需放射性标记时间为40 min,放化纯达98%,比活度为1.5 Ci/μmol; 4 h内,18F-1在PBS和血清中的稳定性均大于96%; 脂水分配系数为logP=-0.995±0.103,表明探针具有较好的水溶性。结果表明18F-1是一个潜在的PET凋亡显像探针,值得进一步研究。
Abstract:
A novel positron emission tomography(PET)molecular probe is designed and prepared for detecting tumor apoptosis. Its physicochemical and biological properties are evaluated. Precursor 1 is obtained by combining the labeling group with the specific peptide sequence Asp-Glu-Val-Asp(DEVD)using the “click chemistry”. Then,one-step 18F-raidolabeling approach is used to acquire the molecular probe 18F-1. Octanol-water partition coefficient and stability of 18F-1 in PBS and serum are investigated. The results show that 18F-1 is obtained within 40 min in good radiochemical purity(>98%)and high specific activity(1.5 Ci/μmol),and the log P value is -0.995±0.103,indicating its characteristic of hydrophilicity. These results suggest that 18F-1 is a potential PET probe and worthy of further investigation.

参考文献/References:

[1] Kerr J F R,Wyllie A H,Currie A R. Apoptosis:a basic biological phenomenon with wide-ranging implications in tissue kinetics[J]. Br J Cancer,1972,18(26):239-257. [2]陈顺军,程兵. 肿瘤细胞凋亡核素显像分子探针研究进展[J]. 国际放射医学核医学杂志,2016,40(2):149-153. Chen Shunjun,Cheng Bing. Progress in molecular probes of radionuclide tumor apoptosis imaging[J]. International Journal of Radiation Medicine and Nuclear Medicine,2016,40(2):149-153. [3]胡四龙,章英剑,周正荣. 凋亡分子影像研究进展[J]. 肿瘤影像学,2013(3):214-219. Hu Silong,Zhang Yingjian,Zhou Zhengrong. Progress on molecular imaging for apoptosis[J]. Oncoradiology,2013(3):214-219. [4]刘秋芳,宋少莉. 核素细胞凋亡显像剂的研究进展[J]. 上海交通大学学报(医学版),2015,35(11):1743-1748. Liu Qiufang,Song Shaoli. Advancces of radionuclide imaging for cell apoptosis[J]. Journal of Shanghai Jiaotong University(Medical Science),2015,35(11):1743-1748. [5]Galluzzi L,Vitale I,Abrams J M,et al. Molecular definitions of cell death subroutines:recommendations of the nomenclature committee on cell death 2012[J]. Cell Death Differ,2012,19(1):107-120. [6]Alam I S,Neves A A,Witney T H,et al. Comparison of the C2A domain of synaptotagmin-I and annexin-V as probes for detecting cell death[J]. Bioconjugate Chemistry,2010,21(5):884-891. [7]Elizabeth A S,Mary T H,Ruth M K,et al. Ordering the cytochrome c-initiated caspase cascade:hierarchical activation of Caspases-2,-3,-6,-7,-8,and-10 in a Caspase-9-dependent manner[J]. The Journal of Cell Biology,1999,144(2):281-292. [8]曲朋,宋利,赵好冬,等. 多肽合成研究进展[J]. 中国现代中药,2015(3):285-289. Qu Peng,Song Li,Zhao Donghao,et al. Research progress of peptide synthesis[J]. Modern Chinese Medicine,2015(3):285-289. [9]张锦明,张晓军,张宝石,等. 自动化“点击合成”正电子标记肽类细胞凋亡显像剂~(18)F-Pen-peptide[J]. 核技术,2011(11):845-850. Zhang Jinming,Zhang Xiaojun,Zhang Baoshi,et al. Automated “click chemistry” synthesis of 18F-Pen-peptide as an apoptosis imaging agent[J]. Nuclear Techniques,2011(11):845-850. [10]Xia C,Chen G,Gangadharmath U,et al. In vitro and in vivo evaluation of the Caspase-3 substrate-based radiotracer[18F]-CP18 for PET imaging of apoptosis in tumors[J]. Molecular Imaging and Biology,2013,15(6):748-757. [11]Shen B,Jeon J,Palner M,et al. Positron emission tomography imaging of drug-induced tumor apoptosis with a caspase-triggered nanoaggregation probe[J]. Angewandte Chemie International Edition,2013,52(40):10511-10514. [12]Liu Z,Pourghiasian M,Radtke M A,et al. An organotrifluoroborate for broadly applicable one-step 18F-labeling[J]. Angewandte Chemie International Edition,2014,53(44):11876-11880. [13]Liu Z,Radtke M A,Wong M Q,et al. Dual mode fluorescent 18F-PET tracers:efficient modular synthesis of rhodamine-[cRGD]2-[18F]-organotrifluoroborate,rapid,and high yielding one-step 18F-labeling at high specific activity,and correlated in vivo PET imaging and ex vivo fluorescence[J]. Bioconjugate Chemistry,2014,25(11):1951-1962. [14]Liu Z,Lin K,Bénard F O,et al. One-step(18)F labeling of biomolecules using organotrifluoroborates[J]. Nature protocols,2015,10(9):1423-1432. [15]Pourghiasian M,Liu Z,Pan J,et al. 18F-AmBF3-MJ9:A novel radiofluorinated bombesin derivative for prostate cancer imaging[J]. Bioorganic & Medicinal Chemistry,2015,23(7):1500-1506. [16]李正超,韩香. 多肽合成方法研究进展[J]. 武警后勤学院学报(医学版),2013,22(2):153-157. Li Zhengchao,Han Xiang. Progress in synthesis methods of peptide[J]. Journal of Logistics University of CAPF(Medical Sciences),2013,22(2):153-157. [17]蒲雯雯. 18F标记Tanaproge衍生物类孕酮受体显像剂的制备及生物学性质的研究[D]. 西安:西北大学理学院,2012. [18]张传宏. 99mTc标记非甾体型孕酮受体显像剂的制备及生物学性质研究[D]. 无锡:江南大学化学与材料工程学院,2014.

备注/Memo

备注/Memo:
收稿日期:2017-01-05 修回日期:2017-03-23 基金项目:江苏省自然科学基金(BK20151118) 作者简介:王伟(1991-),男,硕士生,主要研究方向:分子影像探针,E-mail:wei10060103@163.com; 通讯作者:罗世能(1957-),男,研究员,博士生导师,主要研究方向:药物化学,E-mail:luoshineng@jsinm.org。 引文格式:王伟,林建国,刘桂青,等. 新型肿瘤凋亡显像PET探针的制备与表征[J]. 南京理工大学学报,2018,42(1):107-113. 投稿网址:http://zrxuebao.njust.edu.cn
更新日期/Last Update: 2018-02-28