目的 制备99Tcm标记的含RGD序列的99Tcm-联肼尼克酰胺(HYNIC)-c( RGDfK)环肽单体,评价其在整合素表达阳性的肺腺癌严重联合免疫缺陷(SCID)小鼠肿瘤模型中的生物学分布,并进行显像研究.方法 (1)以HYNIC为双功能螯合剂,以三羟甲基甘氨酸(tricine)和乙二胺二乙酸为协同配体,采用二步法制备99Tcm标记HYNIC-c(RGDfK),进行细胞结合实验,测定标记物生物学活性；(2)将荷A549肺腺癌模型小鼠分为7组[第7组作为竞争性抑制组,注射显像剂前0.5h先注射HYNIC-c(CRDGfk) 100 μg],每组5只,经尾静脉注射7.4 MBq的99Tcm-HYNIC-c (RGDfK),于注射后0.5,1,2,4,8,12h处死,计算荷A549肺腺癌小鼠模型各脏器％ID/g,同时采用ROI技术研究99Tcm-HYNIC-c( RGDfK)在小鼠体内的生物学分布,计算不同时间点的T/NT比值(NT选取肌肉)；(3)取6只荷瘤裸鼠,其中3只为竞争性抑制组,经尾静脉注射7.4 MBq的99Tcm-HYNIC-c (RGDfK),于注射后0.5,1,2,4,8,12 h进行静态γ显像.结果 99Tcm-HYNIC-c (RGDfK)的标记率＞90％,放化纯＞95％.99Tcm-HYNIC-c( RGDfK)与A549肺腺癌细胞特异性结合率最高为36.14％,体内分布实验显示99Tcm-HYNIC-c( RG DfK)在肾的摄取率始终高于20％ID/g,注射后0.5h肿瘤％ID/g为10.52±1.48,8h为17.26 ±2.81,12h为8.93±0.90,竞争性抑制组注射后0.5h为2.29±0.85.通过ROI技术测得T/NT在8h达6.87.注射后1h肿瘤可显影,4～8h显影更清晰.结论 99Tcm标记HYNIC-c (RGDfK)易于制备,具有良好的靶向性.%Objective To synthesize 99Tcm labeled hydrazine-nicotinamide ( HYNIC)-c (RGDfK)and evaluate its biodistribution and imaging in the severe combined immunodeficiency (SCID) nude mice bearing human lung adenocarcinoma.Methods ( 1 )Tcm-HYNIC-c(RGDfK) was prepared by a two-step method using tricine and ethylenediamine diacetate (EDDA) as coligands and HYNIC as the dual functional chelator.The bioactivity of 99Tc m-HYNIC-c (RGDfK) was measured by cell binding experiments.(2) The nude mice bearing human A549 lung adenocarcinoma were randomly divided into 7 groups with 5 in each group.The 7 th group was the competitive inhibition control group and was administrated 100 μg HYNIC -c (RDGfK) 30 min earlier before the injection of 99Tcm-H Y N IC-c ( RGDfK ).The nude mice were scanned at 0.5,1,2,4,8 and 12 h respectively after intravenous injection of 7.4 MBq 99Tcm-HYNIC-c(RGDfK).The biodistribution of the agent was measured as ％ ID/g.The uptake ratio of tumor to muscle (T/NT) was also measured by placing ROI on 99Tcm-HYNIC-c(RGDfK) SPECT imaging.(3)Gamma imaging was performed in 6 mice including 3 in the competitive inhibition control group at 0.5,1,2,4,8 and 12 h post injection.Results The labeling yield of 99Tcm-HYNIC-c(RGDfK) was more than 90％,and the radiochemical purity was more than 95％.99Tcm-HYNIC-c(RGDfK) can specifically bind with A549 adenocarcinoma cells with a binding rate up to 36.14％.Biodistribution study showed that the uptake in the kidney was above 20 ％ ID/g during 0.5 - 8 h post injection.The ％ ID/g in tumor was 10.52 ± 1.48 at 0.5 h,17.26 ±2.81 at 8 h,and 8.93 ±0.90 at 12 h.However,the ％ ID/g in tumor was only 2.29 ±0.85 in the competitive inhibition control group at 0.5 h.The highest T/NT was 6.87 at 8 h by the ROI analysis.Xenograffted tumors could be visualized at 1 h and delineated more clearly from 4 to 8 h post injection of 99Tcm-HYNIC-c(RGDfK).Conclusions 99 Tcm-HYNIC-c (RGDfK) can be readily synthesized.Its binding with A549 lung adenocarcinoma cells is specific and the binding rate is high.
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