CAJ | 학술논문

目的研究新型含RGD的环肽二聚体探针99Tcm-HYNIC-2聚乙二醇(PEG)4-Dimer { Dimer:E-[c(RGDfK)2]}作为整合素αvβ3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γ显像的影响.方法选取整合素αvβ3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αvβ3受体表达情况.制备99Tcm-HYNIC-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(1 mg)恩度,对照组给予同等体积的生理盐水,6h后注射99Tcm-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20 mg/kg恩度和同等体积的生理盐水,给药后行γ显像.采用两样本t检验对实验数据进行统计分析.结果 99 Tcm-HYNIC-2PEG4-Dimer的放化纯大于95％.U87MG细胞高表达整合素αvβ3受体,经恩度处理后整合素αvβ3受体表达逐渐减低,恩度质量浓度为400 μg/ml时,表达程度最低.荷瘤裸鼠注射99Tcm-HYNIC-2PEG4-Dimer后90 min,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)；γ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αvβ3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 99Tcm-HYNIC-2PEG4-Dimer可用于整合素αvβ3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.
목적 연구신형함RGD적배태이취체탐침99Tcm-HYNIC-2취을이순(PEG)4-Dimer { Dimer:E-[c(RGDfK)2]}작위정합소αvβ3수체현상제적가행성,병관찰중조인혈관내피세포억제소주사액(은도)대표기탐침재하류라서체내생물학분포급γ현상적영향.방법 선취정합소αvβ3수체표체양성적인신경효질류세포주U87MG,면역형광검측U87MG경은도처리후적정합소αvβ3수체표체정황.제비99Tcm-HYNIC-2PEG4-Dimer.건립하U87MG신경효질류라서모형,병안간단수궤법장기분위2조,은도조급여200μl(1 mg)은도,대조조급여동등체적적생리염수,6h후주사99Tcm-HYNIC-2PEG4-Dimer,평개탐침재2조하류라서체내적생물학분포.령취하류라서16지,분위은도처리조화생리염수조,분별안체질량급여20 mg/kg은도화동등체적적생리염수,급약후행γ현상.채용량양본t검험대실험수거진행통계분석.결과 99 Tcm-HYNIC-2PEG4-Dimer적방화순대우95％.U87MG세포고표체정합소αvβ3수체,경은도처리후정합소αvβ3수체표체축점감저,은도질량농도위400 μg/ml시,표체정도최저.하류라서주사99Tcm-HYNIC-2PEG4-Dimer후90 min,종류조직유교고섭취,급여은도후종류섭취감저,은도조화대조조종류섭취분별위(1.50±0.08) ％ID/g화(6.27±0.33) ％ID/g(t=40.23,P＜0.05)；γ현상시2조T/NT비치분별위1.02±0.11화2.58±0.36(t=10.25,P＜0.05)；면역조직화학검사결과현시2조정합소αvβ3수체양성표체솔분별위(33.1±2.7)％여(81.5±3.2)％(t=32.60,P＜0.05).결론 99Tcm-HYNIC-2PEG4-Dimer가용우정합소αvβ3수체양성종류적현상,병가용우감측은도료효,유망용우사선은도치료병례.
Objective To study the feasibility of a novel probe 99Tcm-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 immunofluorescence staining before and after treatment with endostar.99Tcm-HYNIC-2PEG4-Dimer was prepared and administered in U87MG tumor bearing mice in 6 h after either administration of endostar (200 μl) or saline (control group) 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 99Tcm-HYNIC-2PEG4-Dimer was exceeded 95％.The expression of integrin αvβ3 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 αvβ3 with the peak effect at the dose of 400 μg/ml.The distribution study in vivo showed that the tracer uptake of U87MG 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 99Tcm-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 ratios 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 radiotracer for integrin αvβ3-positive tumor imaging.It may be used for monitoring the therapeutic effect of endostar and may be potentially used for screening the candidates of anti-angiogenesis therapy.