【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。更多还原

【Abstract】 [Purpose] To investigate the possibility of lymphoma’s antisense imaging with radioiodinated framework region (FR) mRNA antisense oligonucleotides (ASONs). [Methods] An 18-mer 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 tumor-bearing BALB/c mice. SPECT imaging underwent at 0, 1, 2, 24h after injection. Bcl-2 expression in tumor tissue was observed with immunohistochemical method. [Results] The 5′ tyramine group allowed specific and stable radiolabelling of the ASONs with radioiodine. The transduction efficiency in Namalwa cells reached 26.8%±1.54%. When antisense probe injected intratumorally into Namalwa cells bearing mice, the tracer accumulated in tumor tissue. Immunohistochemical analysis showed that antisense group had a Bcl-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.更多还原