中文摘要：

目的：构建多功能分子影像探针——共轭化合物-1,体外标记兔外周血内皮祖细胞（endothelial pro-genitor cells,EPCs）,并进行体内细胞示踪。方法：利用磁共振T1对比剂Gd、近红外荧光染料Cy5.5以及罗丹明合成共轭化合物-1,体外标记EPCs,采用四氮噻唑蓝（MTT）比色实验评价不同浓度bCD-PLL标记EPCs后对细胞增殖力的影响;流式细胞术分析对细胞周期的影响及不同孵育时间细胞荧光标记率。将标记共轭化合物-1的EPCs移植于乳腺癌荷瘤鼠模型,通过磁共振成像和近红外光学成像对移植细胞进行活体示踪。结果：共轭化合物-1的标记对EPCs增殖活性及细胞周期无明显影响;2μmol.L-1共轭化合物-1可有效标记细胞。磁共振成像和近红外光学成像表明标记的EPCs在移植后5 d肿瘤信号出现明显改变。结论：共轭化合物-1能有效标记兔外周血EPCs,细胞活力不受影响。两种活体成像均表明经标记的EPCs移植于乳腺癌荷瘤鼠模型后能够归巢至肿瘤组织,显示出共轭化合物-1的成像优越性。

英文摘要：

Objective： To develop a protein-based multi-modality imaging probe namely bCD-PLL-Cy5.5 Conjugate-1 and to non-invasively monitor probe labeled endothelial progenitor cells（EPCs） in tumor neovascularization.Methods： Bacterial cytosine deaminase（bCD） protein was modified with poly-L-lysine（PLL） that is labeled with imaging reporters including T1 weighted magnetic resonance imaging（MRI） contrast chelator and near infrared（NIR） fluorophore.EPCs isolated from rabbit peripheral blood were labeled with Conjugate-1 by co-culture.Cell proliferation,cell cycling and cell uptake kinetics were evaluated.2×106 labeled cells were transplanted into a MDA-MB-231 tumor bearing mice,both magnetic resonance imaging and near-infrared fluorescence imaging were performed at different time point.Results： Conjugate-1 showed low cytotoxicity in EPCs.The normalized cell viability maintained above 90% after incubation for 1-5 days.Flow cytometry studies demonstrated cells were effectively labeled in 24 hours.After cell transplantation,signal enhancement of tumors in T1WI and significant reduction of T1 relaxation time were obtained from MRI.NIR optical imaging also demonstrated the ＂homing＂ EPCs in tumor area.Conclusion： As a multimodal imaging contrast media,Conjugate-1 offers a promising imaging probe for tracking the delivery of EPCs in tumor models.