【摘要】 目的：探讨用放射性碘标记的框架区（framework region mRNA．FR）mRNA 反义寡核苷酸（antisense oligo-nucleotide，ASON）作为 B 细胞淋巴瘤反义显像剂及反义治疗药物的可能性 方法：通过氯胺-T 法用碘[¹²⁵I 与碘[¹³¹I]标记含酪胺的18聚体寡核苷酸获得¹²⁵I-或¹³¹I-FR-ASON，建立荷人淋巴瘤裸鼠动物模型 将148 kBq¹²⁵I-FR-ASON（2～μg）经尾静脉注入正常小鼠，于不同时间处死小鼠，测定不同组织及标准源的放射性计数 荷瘤裸鼠瘤内注入脂质体包裹的3.33 MBq ¹³¹I-FR-ASON（7～9μg），分别于注射后不同时间进行单光子发射计算机断层（single photon emission computer tomographv,SPECT）显像，以脂质体包裹的正义寡核苷酸作为对照，24h 显像后处死裸鼠，取出血液、重要器官和肿瘤组织，测定各组织的放射性计数，并计算每克组织摄取率及肿瘤与非瘤组织放射性摄取比值（T/NT） 结果：¹²⁵I-FR-ASON 注入正常小鼠体内后1h．各脏器的放射性摄取达高峰，24h 基本清除 肝、胃和肠放射性分布最高，骨、肌肉、脑中放射性分布较少 荷瘤裸鼠瘤内注入脂质体包裹的¹³¹I 标记 ASON后立即用 SPECT 成像仅见肿瘤部位，1和2h 成像可见小踪剂从肿瘤到腹腔，24h 仍可见肿瘤显像 比较24h 反义组与正义组更多还原

【Abstract】 Objective:To investigate the possibility of using radioiodine labeled framework region(FR)antisense oligonucleotides(ASONs)as an imaging agent or antisense therapeutic radiopharmaceu-tical in lymphoma.Methods:A 18-mer partial phosphorothioate oligonucleotide sequence was synthe-sized and grafted in 5’with a tyramine group which was further radioiodinated.Radioiodination of the tyra-mine derivatized oligonucleotides was performed using the chloramine T method.(1)Normal CD-1 micewere injected via a tail vein with 148 kBq (125)~I-FR-ASON(2-3μg).Animals were sacrificed at the endof 1,2,4 and 24h,and tissue samples were studied.(2)Liposome-mediated 3.33 MBq (131)I-FR-ASON(7-9μg)were injected intralumorally into tumor-bearing BALB/c mice(6 weeks after innculation of10~7 Namalwa cells)meanwhile liposome-mediated (131)~I labeled sense oligonucleotides served as controls.Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24h afterinjection.Percentage of the injected dose per gram of tumor and tumor/non-tumor tissue ratios(T/NT)were calculated tot each group of mice and the difference between two groups was assessed.Results:The5′tyramine group allowed specific and stable radinlabeling of the ASON with radioiodine.The radioactivi-ty reached its peak 1h after injection,and then decreased rapidly in normal mice after intravenous ad-ministration of (125)~I-FR-ASON.The liver,stomach and intestine played an important role in biodistributionand radioactivity counts were low in bone,brain and blood.When (131)I-FR-ASON was injected intratumor-ally into mice grafted with Namalwa cell line,images showed the tracer accumulated in the tumor,Imme-diately after intratumoral administration,only the tumor was visible.Scintiscans performed at the end of 1and 2h showed elimination of the tracer from the tumor to the abdomen and at the end of 24h the tumorwas clearly seen.Percentage of the injected dose per gram of tumor and T/NT ratios for the sense group(control)were significantly lower than those of the antisense group.Conclusion:Radiolabeled Ig FRASON showed high specificity in V1 family B-cell lymphoma,which should be further investigated for nu-clear medicine imaging application and radionuclide antisense therapy.更多还原