摘要
目的 探索以核医学方法对甲状腺未分化癌(anaplastic thyroid carcinoma,ATC)细胞的端粒酶活性进行体内显像的可行性.方法 采用甲状腺未分化癌细胞(ARO)建立荷瘤裸鼠模型,以1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(1,4,7,10-Tetraazacyclododecane-N,N’,N”,N(”’)-tetraacetic acid,DOTA)作为双功能螯合剂对人端粒酶逆转录酶反义寡核苷酸(human telomerase reverse transcriptase antisense oligonucleotide,hTERT ASON)进行99mTc间接标记,制备DOTA-hTERT ASON,并对肿瘤模型进行单光子发射计算机断层显像(single photon emission computed tomography,SPECT)显像.结果 99mTc-DOTA-hTERT ASON对ARO移植瘤具有良好的靶向性,最佳显像时间为注射后2～8h.结论 99mTc-DOTA-hTERT ASON可对活体内ATC细胞的端粒酶进行检测,在ATC的诊断及治疗方面具有潜在的价值.
Objective To develop a method of detecting the telomerase activity of anaplastic thyroid carcinoma(ATC) in vivo with nuclear medicine imaging. Methods Human telomerase reverse transcriptase antisense oligonucleotide( hTERT ASON) was labeled with technetium-99m(99mTc)though a bifunctional chelator 1,4,7,10-Tetraazacyclododecane-N,N',N″,N-tetraacetic acid(DOTA); and then tumor bearing BALB/c nude mouse models were established with anaplastic thyroid carcinoma ARO cell line; finally,the radiolabeled antisense probes were injected into model mouses through tail vein and planer scan was performed through single photon emission computed tomography( SPECT) at different time point after injection,48 hrs after imaging all animals were sacrificed and immunohistochemical staining was used to detect the activity of telomerase of ARO tumors. Results 99mTc-DOTA-hTERT ASON can home to ARO tumors and the tumors can be clearly displayed at 2-8h after injection and the highest tumor to nontarget ratio( T /NT) can reach 2. 0; telomerase is highly expressed in ARO tumors and can be depressed by DOTA-hTERT ASON. Conclusion 99mTc-DOTA-hTERT ASON can be used as a potential probe in detecting telomerase activity of ATC cells in vivo and diagnosing and treating patients with ATC as well.
出处
《中国生化药物杂志》
CAS
北大核心
2014年第5期167-170,共4页
Chinese Journal of Biochemical Pharmaceutics
基金
云南省联合基金项目(2010CD149)
关键词
99mTc
甲状腺未分化癌
端粒酶
反义显像
Technetium-99m
anaplastic thyroid carcinoma
telomerase
antisense imaging
