核素示踪框架区反义寡核苷酸对V1家族B细胞淋巴瘤识别特异性的研究  

Specific Identification to V1 Family B-cell Lymphoma with Radionuclide Tracing Framework Region Antisense Oligonucleotides

作　　者：沈晶[1] 王荣福[1] 张春丽[1] 刘萌[1] 

机构地区：[1]北京大学第一医院,北京100034

出　　处：《肿瘤学杂志》2008年第8期644-647,共4页Journal of Chinese Oncology

基　　金：国家重点基础研究发展计划基金-973计划(2006CB705705);国家自然科学基金(30270410;30470498;30670583);北京大学985Ⅱ期基金(985-2-056);高等学校博士点学科专项科研基金(20050001108)

摘　　要：[目的]探讨用放射性碘标记的框架区mRNA(framework region,FR mRNA)反义寡核苷酸(antisense oligonucleotide,ASONs)作为淋巴瘤的反义显像剂的可能性。[方法]合成5′含酪胺的硫磷修饰的18聚体寡核苷酸,并通过氯胺-T法用放射性碘标记。用脂质体包裹125I-FR-ASONs转导Namalwa(V1家族B细胞淋巴瘤)和HL-60(人髓性白血病)细胞,并比较转导效率。荷瘤BALB/C鼠瘤内注入脂质体包裹的131I-FR-ASONs,分别于注射后0、1、2、24h进行SPECT显像。免疫组化分析肿瘤组织Bcl-2表达情况。[结果]5′含酪胺的ASONs能用放射性碘稳定标记,在Namalwa细胞中的转导效率达26.8%±1.54%。反义探针瘤内注入荷Namalwa细胞裸鼠中,示踪剂特异性浓聚在肿瘤组织。免疫组化分析表明反义组肿瘤组织Bcl-2染色较弱。[结论]放射性碘标记的FRASONs基因可特异性识别V1家族B细胞淋巴瘤,有望用于淋巴瘤反义显像和反义治疗的研究。[Purpose] To investigate the possibility of lyrnphoma＇s antisense imaging with radioiodinated framework region （FR） rnRNA antisense oligonucleotides （ASONs）. [Methods] An 18-rner partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5＇ with a tyramine group which was further radioiodinated with the chloramine T method. The Namalwa （V1 family B-cell lymphoma） and HL-60 （acute myeloid leukemia） cells were transducted with liposome-mediated ^125I-FR-ASONs, and the transduction efficiencies were compared. Liposome-mediated ^131I-FR-ASONs were injected intratumorally into turnor-bearing BALB/c mice. SPECT imaging underwent at 0, 1, 2, 24h after injection. Bel-2 expression in tumor tissue was observed with imrnunohistochernical method. [Results] The 5＇ tyrarnine group allowed specific and stable radiolabelling of the ASONs with radioiodine. The transduetion efficiency in Narnalwa cells reached 26.8%±1.54%. When antisense probe injected intraturnorally into Narnalwa cells bearing mice, the tracer accumulated in tumor tissue. Irnrnunohistochernical analysis showed that antisense group had a Bel-2 weak stain. [Conclusion] Radioiodinated FR ASONs gene could specifically identify to V1 family B-cell lymphoma. It could use to antisense imaging and antisense therapy for lymphoma.

关 键 词：淋巴瘤 寡核苷酸 放射性核素 标记 反义显像 

分 类 号：R730.44[医药卫生—肿瘤]