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[目的]评价脂质体介导对反义分子探针在体外靶细胞摄取以及在荷瘤裸鼠体内特异显像的不同影响情况。[方法]以双功能螯合剂法,制备99mTc标记的针对人端粒酶催化亚单位(hTERT)mRNA的正、反义探针。分别测定在有/无脂质体介导下,不同处理组的细胞对分子探针的摄取率。建立荷MCF-7乳腺癌裸鼠模型,分别经尾静脉注射有/无脂质体介导的正、反义探针。注射后6h对所有裸鼠进行SPECT显像,分别勾画肿瘤部位与对侧相应部位的感兴趣区,定量分析不同处理组的肿瘤放射性摄取情况。[结果]分子探针的标记率达到76%±5%,放射性化学纯度达到96%以上,比活度达到1850kBq/μg。不论脂质体介导与否,反义探针在不同时相的细胞摄取率均高于正义探针(P<0.05);脂质体明显提高细胞对分子探针的摄取,最高可达2.5倍。通过脂质体介导,细胞对反义探针的摄取高峰值提前至2h,并保持稳定水平至3h。荷瘤裸鼠体内显像结果显示:不论脂质体介导与否,反义组的荷瘤裸鼠肿瘤部位可见有明显的放射性浓聚,而正义组的荷瘤裸鼠肿瘤部位未见有明显的放射性浓聚;脂质体介导没有明显增加肿瘤/非肿瘤(T/NT)比值(P>0.05)。[结论]脂质体在体外能有效地提高分子探针的细胞靶向摄取效率,但是对分子探针在体内的显像效果无明显影响作用。
[Objective] To evaluate the different effects of liposome-mediated targeting of antisense molecular probes on target cells in vitro and their specific imaging in tumor-bearing nude mice. [Method] The bimodal chelator method was used to prepare the positive and antisense probes of 99mTc labeled human telomerase catalytic subunit (hTERT) mRNA. The rate of uptake of molecular probes by different treatment groups in the presence / absence of liposomes was determined, respectively. The MCF-7 breast cancer nude mice model was established and the positive and negative antisense probes mediated by liposomes were injected through tail vein respectively. All the nude mice were subjected to SPECT imaging 6h after injection, and the regions of interest of the tumor site and the contralateral side were sketched separately to quantitatively analyze the tumor radioactivity uptake in different treatment groups. [Result] The labeling rate of molecular probe reached 76% ± 5%, the radiochemical purity reached 96% and the specific activity reached 1850kBq / μg. Liposome-mediated or not, the cell uptake rate of antisense probe in different phases was higher than that of the sense probe (P <0.05); liposomes significantly increased the uptake of molecular probes up to 2.5 Times By liposome-mediated, the peak of the uptake of antisense probe by the cells was advanced to 2h and remained stable to 3h. Tumor bearing nude mice in vivo imaging results show that: whether liposome-mediated or not, antisense group of tumor-bearing nude mice showed significant radioactive accumulation of tumor, while the tumor-bearing nude mice in the sense of the group had no tumor sites Significant radioactive concentration; liposome-mediated no significant increase in tumor / non-tumor (T / NT) ratio (P> 0.05). [Conclusion] The liposome can effectively enhance the cell-targeted uptake efficiency of molecular probes in vitro, but has no obvious effect on the imaging effect of molecular probes in vivo.