目的：microRNA-155（miR-155）显著高表达于乳腺癌、肺癌、肝癌等多种恶性肿瘤，本研究旨在构建靶向miR-155的放射性示踪探针对乳腺肿瘤的活体显像。方法：体外化学合成靶向miR-155的反义互补寡核苷酸探针（AMO-155），并对其进行5′端乙酰基修饰及2′甲氧基修饰,进而与双功能螯合剂NHSMAG3偶联后，在氯化亚锡的还原作用下对其标记 99mTc，评价血清稳定性，并对乳腺癌荷瘤裸鼠进行活体显像，对比反义、无义及阻断组的显像差异，并通过实时定量PCR（quantitative real-time PCR, qRT-PCR）鉴定肿瘤的miR-155水平。结果：99mTc-AMO-155的制备标记率达97%（n=5），放射化学纯度大于98%（n=5），放射比活度约为3.75 GBq/μg。通过对比无义对照组及阻断组，99mTc-AMO-155能够在活体水平特异性地显示miR-155高表达的恶性肿瘤。此外，针对miR-155不同表达水平的肿瘤，99mTc-AMO-155亦可在活体水平反映其表达差异。结论：经化学修饰的99mTc标记的AMO-155探针具有良好的血清稳定性及活体肿瘤靶向识别作用，为肿瘤显像提供了潜在的新型探针。

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 oligonu-cleotide (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.