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南方医科大学南方医院 核医学科,广州,510515
[ "作者简介:齐永帅,男,1988年出生,2012年毕业于济宁医学院,现为南方医科大学在读硕士研究生,研究方向为影像医学" ]
[ "通讯作者: 李贵平,E-mail: ligp62@126.com E-mail:ligp62@126.com" ]
纸质出版日期:2014-09-09
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齐永帅, 黄宝丹, 杜 丽, 等. 脑胶质瘤U87-EGFRvIII细胞反义寡核苷酸的188Re标记实验研究[J]. 核技术, 2014,37(9):090301
QI Yongshuai, HUANG Baodan, DU Li, et al. Experimental study on the labeling of antisense oligonucleotide from U87-EGFRvIII glioma cells with 188Re[J]. Nuclear techniques, 2014, 37(9): 090301
齐永帅, 黄宝丹, 杜 丽, 等. 脑胶质瘤U87-EGFRvIII细胞反义寡核苷酸的188Re标记实验研究[J]. 核技术, 2014,37(9):090301 DOI: 10.11889/j.0253-3219.2014.hjs.37.090301.
QI Yongshuai, HUANG Baodan, DU Li, et al. Experimental study on the labeling of antisense oligonucleotide from U87-EGFRvIII glioma cells with 188Re[J]. Nuclear techniques, 2014, 37(9): 090301 DOI: 10.11889/j.0253-3219.2014.hjs.37.090301.
研究放射性核素铼(188Re)标记脑胶质瘤U87-EGFRvIII(Epidermal Growth Factor Receptor Variant III)细胞反义寡核苷酸序列的制备方法,探讨其作为脑胶质瘤反义显像剂的可能性。采用细胞指数富集的配基系统进化技术(Cell-based Systematic Evolution of Ligands by Exponential Enrichment
Cell-SELEX)筛选脑胶质瘤U87-EGFRvIII细胞,得到一段高亲和力的反义寡核苷酸序列U2,然后采用直接标记法进行188Re的放射性标记,按照正交实验设计进行188Re最佳标记条件的摸索,纸层析法测定标记率,通过体外稳定性实验评价188Re-U2的放化特性,测定标记物静脉注射后在大耳兔不同时相血液放射性清除曲线,应用SPECT显像观察标记物在兔体内的放射性动态分布变化。结果表明:在最佳标记条件下188Re-U2的标记率为70%±14%;经Sep-PaK C18反相柱分离纯化后,188Re-U2在生理盐水和血清中37 ºC下放置24 h的放化纯度分别为70.6%和95.55%;188Re-U2在兔体内的血放射性清除迅速,主要通过肾脏排泄,其余脏器内放射性均较低。188Re直接法标记U87-EGFRvIII细胞反义寡核苷酸U2的方法简单,具有良好的标记率和体内外稳定性,并且体内分布动力学特性也比较理想。
Background: Gliomas
originating from glial cells
are the most common neoplasms affecting the central nervous system
and glioblastoma multiforme is the most malignant subtype of glioma. The classical subtype of glioblastoma is defined by epidermal growth factor receptor (EGFR) gene amplification
and glioblastomas bearing EGFR amplifications often express EGFRvIII. This suggests that EGFRvIII may operate as critical drivers in the genesis of glioblastoma
hence representing ideal targets for targeted anticancer therapies. Purpose: The aim is to establish a radiolabeling method of antisense oligonucleotide (U2) from U87-EGFRvIII glioma cells with radionuclide rhenium (188Re) and to investigate the possibility of using 188Re-U2 as imaging agents for brain glioma. Methods: A high affinity of antisense oligonucleotide sequences U2 from U87-EGFRvIII glioma cells was screened by the cell systematic evolution of ligands by exponential enrichment
and was directly labeled with 188Re. The optimal labeling condition and stability in vitro were investigated by an orthogonal experimental design method. Labeling rates were determined by paper chromatography. Blood radioactivity clearance of 188Re-U2 in rabbits was evaluated by determining blood radioactive concentrations at different time points after injection of 188Re-U2
and its dynamic distribution was investigated by SPECT imaging. Results: Antisense oligonucleotide (U2) was successfully radiolabeled with 188Re and the labeling rate of 188Re-U2 was 70%±14%. After purification of the labeled 188Re-U2 with Sep-PaK C18 reversed phase extraction cartridge
the radiochemical purity was 70.6% after placing in physiological saline for 24 h and 95.55% after incubation at 37 ºC with human serum. SPECT imaging showed that 188Re-U2 could be quickly cleared from the blood in normal animals primarily through the kidneys
and the radioactivity in other tissues and organs remained low. Conclusion: This method of directly labeling antisense oligonucleotide (U2) with 188Re is simple with better labeling efficiency and stability both in vitro and in vivo
and so 188Re-U2 has more ideal biodistribution and biokinetics in vivo.Cited
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