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Improved synthesis and biological evaluation of Tc‐99m radiolabeled AMO for miRNA imaging in tumor xenografts
Author(s) -
Kang Lei,
Fan Zhongyi,
Sun Hongwei,
Feng Yingying,
Ma Chao,
Yan Ping,
Zhang Chunli,
Ma Huan,
Hao Pan,
Chen Xueqi,
Zheng Zhibing,
Xu Xiaojie,
Wang Rongfu
Publication year - 2015
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3351
Subject(s) - chemistry , microrna , radiochemistry , cancer research , biochemistry , gene , biology
MicroRNAs (miRNAs) have been considered as important biomarkers for malignant tumors. In this study, we introduced an improved 99m Tc labeling method for noninvasive visualization of overexpressed miRNAs in tumor‐bearing mice. Anti‐miRNA‐21 oligonucleotide (AMO) with partial 2′‐O‐methyl and phosphorothioate modification was designed and chemically synthesized. After conjugated with NHS‐MAG3, AMO was labeled with 99m Tc. Optimization was made to shorten reaction time and to improve labeling efficiency. Labeling efficiency was 97%, and specific activity was 2.78 MBq/ng. During 12 h, 99m Tc‐AMO showed no significant degradation by gel electrophoresis. Its radiochemical purity was stable, between 95.8% and 99.1%. Further, 99m Tc‐AMO decreased the level of miR‐21 and increased the expression of PTEN protein at cellular level, shown by qRT‐PCR and Western blot. Fluorescent protein labeled AMO displayed specific distribution and good stability in tumor cells. After the administration in tumor‐bearing mice, 99m Tc‐AMO showed more radioactive uptake in the miR‐21 over‐expressed tumors than scramble control. Biodistribution results further proved the significant difference of tumor uptake between 99m Tc‐AMO and 99m Tc‐control. Therefore, this study presents an improved method with shorten time to prepare a 99m Tc radiolabeled AMO. In addition, it supports the role of 99m Tc‐AMO for noninvasive visualization of miR‐21 in malignant tumors.