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目的应用GoldMagTM-CS纳米金磁微粒标记含RGD序列的环形多肽[cyclic arginine-glycine-aspartic-D-phenylalanine-lysine,c(RGDfK))]构建靶向肿瘤新生血管特异性分子探针并探讨其在体内MR成像的可行性。方法通过GoldMagTM-CS纳米金磁微粒与c(RGDfK)非共价键偶联方法构建特异性分子探针(RGD@GOLDMag)。利用流式细胞术观察RGD@GOLDMag与人脐静脉内皮细胞(HUVECs)结合的特异性。建立MR扫描序列,根据孵育HUVECs的探针的不同,分为A阳性组(RGD@GOLDMag孵育)、B阴性对照组(无关抗体和金磁颗粒耦合成的探针孵育)和C竞争抑制对照组[预先加入c(RGDfK)3、0 min后再加入RGD@GOLDMag孵育],另外设立2个空白对照组D及E(试管中只加水或凝胶)。利用临床应用的3.0 T磁共振扫描仪进行MR成像,观察其对磁共振信号的影响。结果成功构建了靶向血管生成的特异性MR分子探针;构建的MR分子探针能与HUVECs特异性地结合;并可显著降低T2*序列信号。竞争抑制对照组及阴性对照组信号无明显改变,信号差异具有统计学意义(P<0.05)。结论应用纳米金磁微粒及c(RGDfK)构建的MR分子探针能在临床应用的3.0 T磁共振扫描仪特异性的靶向肿瘤血管生成,有望应用于活体肿瘤新生血管的特异性显像。
OBJECTIVE: To construct tumor targeting neovascular-specific molecular probes using goldMagTM-CS nanogold magnetism particles labeled cyclic polypeptide containing RGD sequence [c (RGDfK)]] MR imaging in vivo feasibility. Methods The specific molecular probe (RGD @ GOLDMag) was constructed by non-covalent coupling of goldMagTM-CS nano-particles and c (RGDfK). The specificity of RGD @ GOLDMag binding to human umbilical vein endothelial cells (HUVECs) was observed by flow cytometry. The MR scanning sequence was established and divided into A positive group (RGD @ GOLDMag incubation), B negative control group (probe coupling of irrelevant antibody and gold magnetic particles) and C competitive inhibition control group according to the different probes for HUVECs incubation [Preincubation of c (RGDfK) for 3 min followed by RGD @ GOLDMag incubation] and two blank control groups, D and E, were set up (water or gel in tubes only). MR imaging was performed with a clinical application of 3.0 T magnetic resonance scanner to observe its influence on magnetic resonance signals. Results The specific MR probes targeting angiogenesis were successfully constructed. The constructed MR probes could specifically bind to HUVECs and significantly reduce the T2 * signal. The signal of competitive inhibition group and negative control group had no significant change, the difference of signal had statistical significance (P <0.05). CONCLUSION: MR molecular probes constructed with nanogold magnetite particles and c (RGDfK) can specifically target tumor angiogenesis in clinically applied 3.0 T MRI scanners, and are expected to be used in specific imaging of neoplasms of living tumors.