中文摘要：

目的研究新型含RGD的环肽二聚体探针^99Tc^m-HYNIC-2聚乙二醇（PEG）4-Dimer{Dimer：E-[C（RGDfK）：]}作为整合素αv β3受体显像剂的可行性，并观察重组人血管内皮细胞抑制素注射液（恩度）对标记探针在荷瘤裸鼠体内生物学分布及1显像的影响。方法选取整合素αv β3受体表达阳性的人神经胶质瘤细胞株U87MG，免疫荧光检测U87MG经恩度处理后的整合素αv β3受体表达情况。制备^99Tc^mHYNIC．2PEG4-Dimer。建立荷U87MG神经胶质瘤裸鼠模型，并按简单随机法将其分为2组，恩度组给予200μl（1rag）恩度，对照组给予同等体积的生理盐水，6h后注射^99Tc^m-HYNIC．2PEG4-Dimer，评价探针在2组荷瘤裸鼠体内的生物学分布。另取荷瘤裸鼠16只，分为恩度处理组和生理盐水组，分别按体质量给予20mg／kg恩度和同等体积的生理盐水，给药后行1显像。采用两样本t检验对实验数据进行统计分析。结果^99Tc^m-HYNIC．2PEG4-Dimer的放化纯大于95％。U87MG细胞高表达整合素αv β3受体，经恩度处理后整合素αv β3受体表达逐渐减低，恩度质量浓度为400μg／ml时，表达程度最低。荷瘤裸鼠注射^99Tc^m-HYNIC-2PEG4-Dimer后90min，肿瘤组织有较高摄取，给予恩度后肿瘤摄取减低，恩度组和对照组肿瘤摄取分别为（1．50±0．08）％ID／g和（6．27±0．33）％ID／g（t=40．23，P〈0．05）；1显像示2组T／NT比值分别为1．02±0．11和2．58±0．36（t=10．25，P〈0．05）；免疫组织化学检查结果显示2组整合素αv β3受体阳性表达率分别为（33．1±2．7）％与（81．5±3．2）％（t=32．60，P〈0．05）。结论^99Tc^m-HYNIC-2PEG-4Dimer可用于整合素αv β3受体阳性肿瘤的显像，并可用于监测恩度疗效，有望用于筛选恩度治疗病例。

英文摘要：

Objective To study the feasibility of a novel probe ^99Tc^m-HYNIC-2 （poly-（ ethylene glycol）, PEG） 4-Dimer（ Dimer： E- [ c （RGDfK） 2 ] ） as a potential imaging agent for integrin αv β3 positive tumors, and also to observe the influence of an angiogenesis inhibitor, endostar, on the biodistribution and tumor uptake of the tracer in tumor bearing nude mice. Methods The expression of integrin αv β3 in human glioma cells U87MG was determined with immunofluoreseence staining before and after treatment with en- dostar. ^99Tc^m-HYNIC-2PEG4-Dimer was prepared and administered in U87MG tumor bearing mice in 6 h af- ter either administration of endostar （200 td ） or saline （control axouo ） and then biodistribution study was performed. Other 16 mice were divided into endostar treated group （20 mg/kg） and control group （saline） and then gamma imaging was performed in the two groups. Statistical significance of differences between the two groups was assessed using two-sample t test. Results Radiochemical purity of ^99Tc^m-HYNIC-2PEG4- Dimer was exceeded 95%. The expression of integrin etvl33 in U87MG cell was high and gradually decreased after treatment with endostar. There was a negative dose-effect relationship between the dose of endostar and the expression of integrin αv β3 with the peak effect at the dose of 400 μg/ml. The distribution study in vivo showed that the tracer uptake of Ug7MG tumors was high, but it decreased after injection of endostar. At 90 min, the %ID/g of endostar and control groups were 1.50±0.08 and 6.27±0. 33, respectively （t= 40.23, P〈 0. 05）. The average T/NT ratios of ^99Tc^m-HYNIC-2PEG4-Dimer uptake in the endostar and control groups were 1.02±0.11 and 2.58±0.36, respectively （t = 10.25, P〈0.05）. The integrin αv β3 positive expression ra- tios of tumor in endostar and control groups were （33.1±2.7） % and （ 81.5±3.2） %, respectively （ t = 32.60, P〈0.05）. Conclusions The novel probe 99Tcm-HYNIC-2PEG4-Dimer may be a promising