In vivo imaging of breast tumors by a 99mTc radiolabeled probe targeting microRNA-155 in mice models.
- Author:
Lei KANG
1
;
Yan HUO
1
;
Rong Fu WANG
1
;
Chun Li ZHANG
1
;
Ping YAN
1
;
Xiao Jie XU
2
Author Information
1. Department of Nuclear Medicine, Peking University First Hospital, Beijing 100034, China.
2. Department of Medical Molecular Biology, Beijing Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100850, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Breast Neoplasms/diagnostic imaging*;
Cell Line, Tumor;
Female;
Humans;
Mice;
MicroRNAs/analysis*;
Oligonucleotides, Antisense;
Oligopeptides;
Radiopharmaceuticals;
Succinimides;
Technetium;
Tissue Distribution
- From:
Journal of Peking University(Health Sciences)
2018;50(2):326-330
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:MicroRNA-155 (miR-155) is significantly highly expressed in breast cancer, lung cancer, liver cancer and other malignant tumors. This study was to design and construct a radiolabeled probe targeting miR-155 for in vivo imaging in breast cancer.
METHODS:Anti-miR-155 oligonucleotide (AMO-155) was chemically synthesized with 2' OMe modification. Its 5' end was linked with acetyl amine group. After chelated with a bifunctional chelator NHS-MAG3, AMO-155 was radiolabeled with 99mTc using stannous chloride. The serum stability was evaluated at cellular level. In vivo imaging was performed in MCF-7 tumor bearing mice after the administration of 99mTc radiolabeled AMO-155 and scramble control probes, respectively. Furthermore, the blocked imaging of tumor bearing mice was obtained after the injection of unlabeled AMO-155 2 hours ahead. MCF-7 and MDA-MB-231 tumor bearing mice with different expression level of miR-155 were imaged, respectively. Quantitative real-time PCR (qRT-PCR) was used to identify the expression level of miR-155 in the bearing tumors.
RESULTS:99mTc-AMO-155 was prepared with high radiolabeled efficiency (97%), radiochemical purity (greater than 98%), and radioactive specific activity (3.75 GBq/μg). 99mTc-AMO-155 was stable in fresh human serum for 12 hours. After the administration via tail vein, 99mTc-AMO-155 displayed significant accumulation in MCF-7 bearing tumors with high expression level of miR-155, whereas 99mTc-control showed little accumulation. After blocked with unlabeled AMO-155, the tumor could not be visualized clearly after the administration of 99mTc-AMO-155. Furthermore, 99mTc-AMO-155 could show the differential expression of miR-155 in vivo. MCF-7 tumor was shown with significantly higher radioactive accumulation than MDA-MB-231, based on its higher expression level of miR-155, which was verified by qRT-PCR.
CONCLUSION:99mTc-labeled AMO-155 with chemical modification showed good serum stability and in vivo tumor targeting ability. This study provides a potential probe for in vivo imaging of breast cancer.
