中华核医学杂志
中華覈醫學雜誌
중화핵의학잡지
CHINESE JOURNAL OF NUCLEAR MEDICINE
2011年
6期
405-409
,共5页
锁耀宇%杨卫东%马晓伟%梁晓燕%马温惠%汪静
鎖耀宇%楊衛東%馬曉偉%樑曉燕%馬溫惠%汪靜
쇄요우%양위동%마효위%량효연%마온혜%왕정
肽类,环%锝%同位素标记%放射性核素显像%肺肿瘤%肿瘤细胞,培养的%小鼠,裸
肽類,環%锝%同位素標記%放射性覈素顯像%肺腫瘤%腫瘤細胞,培養的%小鼠,裸
태류,배%득%동위소표기%방사성핵소현상%폐종류%종류세포,배양적%소서,라
Peptids,cyclic%Technetium%Isotope labeling%Radionuclide imaging%Lung neoplasms%Tumor cells,cultured%Mice,nude
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.
目的 製備99Tcm標記的含RGD序列的99Tcm-聯肼尼剋酰胺(HYNIC)-c( RGDfK)環肽單體,評價其在整閤素錶達暘性的肺腺癌嚴重聯閤免疫缺陷(SCID)小鼠腫瘤模型中的生物學分佈,併進行顯像研究.方法 (1)以HYNIC為雙功能螯閤劑,以三羥甲基甘氨痠(tricine)和乙二胺二乙痠為協同配體,採用二步法製備99Tcm標記HYNIC-c(RGDfK),進行細胞結閤實驗,測定標記物生物學活性；(2)將荷A549肺腺癌模型小鼠分為7組[第7組作為競爭性抑製組,註射顯像劑前0.5h先註射HYNIC-c(CRDGfk) 100 μg],每組5隻,經尾靜脈註射7.4 MBq的99Tcm-HYNIC-c (RGDfK),于註射後0.5,1,2,4,8,12h處死,計算荷A549肺腺癌小鼠模型各髒器％ID/g,同時採用ROI技術研究99Tcm-HYNIC-c( RGDfK)在小鼠體內的生物學分佈,計算不同時間點的T/NT比值(NT選取肌肉)；(3)取6隻荷瘤裸鼠,其中3隻為競爭性抑製組,經尾靜脈註射7.4 MBq的99Tcm-HYNIC-c (RGDfK),于註射後0.5,1,2,4,8,12 h進行靜態γ顯像.結果 99Tcm-HYNIC-c (RGDfK)的標記率＞90％,放化純＞95％.99Tcm-HYNIC-c( RGDfK)與A549肺腺癌細胞特異性結閤率最高為36.14％,體內分佈實驗顯示99Tcm-HYNIC-c( RG DfK)在腎的攝取率始終高于20％ID/g,註射後0.5h腫瘤％ID/g為10.52±1.48,8h為17.26 ±2.81,12h為8.93±0.90,競爭性抑製組註射後0.5h為2.29±0.85.通過ROI技術測得T/NT在8h達6.87.註射後1h腫瘤可顯影,4～8h顯影更清晰.結論 99Tcm標記HYNIC-c (RGDfK)易于製備,具有良好的靶嚮性.
목적 제비99Tcm표기적함RGD서렬적99Tcm-련정니극선알(HYNIC)-c( RGDfK)배태단체,평개기재정합소표체양성적폐선암엄중연합면역결함(SCID)소서종류모형중적생물학분포,병진행현상연구.방법 (1)이HYNIC위쌍공능오합제,이삼간갑기감안산(tricine)화을이알이을산위협동배체,채용이보법제비99Tcm표기HYNIC-c(RGDfK),진행세포결합실험,측정표기물생물학활성；(2)장하A549폐선암모형소서분위7조[제7조작위경쟁성억제조,주사현상제전0.5h선주사HYNIC-c(CRDGfk) 100 μg],매조5지,경미정맥주사7.4 MBq적99Tcm-HYNIC-c (RGDfK),우주사후0.5,1,2,4,8,12h처사,계산하A549폐선암소서모형각장기％ID/g,동시채용ROI기술연구99Tcm-HYNIC-c( RGDfK)재소서체내적생물학분포,계산불동시간점적T/NT비치(NT선취기육)；(3)취6지하류라서,기중3지위경쟁성억제조,경미정맥주사7.4 MBq적99Tcm-HYNIC-c (RGDfK),우주사후0.5,1,2,4,8,12 h진행정태γ현상.결과 99Tcm-HYNIC-c (RGDfK)적표기솔＞90％,방화순＞95％.99Tcm-HYNIC-c( RGDfK)여A549폐선암세포특이성결합솔최고위36.14％,체내분포실험현시99Tcm-HYNIC-c( RG DfK)재신적섭취솔시종고우20％ID/g,주사후0.5h종류％ID/g위10.52±1.48,8h위17.26 ±2.81,12h위8.93±0.90,경쟁성억제조주사후0.5h위2.29±0.85.통과ROI기술측득T/NT재8h체6.87.주사후1h종류가현영,4～8h현영경청석.결론 99Tcm표기HYNIC-c (RGDfK)역우제비,구유량호적파향성.
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.
