CAJ | 학술논문

目的制备68 Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-环状NGR(DOTA-cNGR),并评价其在正常小鼠体内的生物分布及对荷肺腺癌裸鼠的靶向显像能力.方法以羟乙基哌嗪乙硫磺酸(HEPES)为缓冲体系(pH值5.0),水浴合成68Ga-DOTA-cNGR,HPLC测定标记率及放化纯,观察其在人血清中的稳定性.进行68 Ga-DOTA-cNGR的正常小鼠体内生物分布和荷肺腺癌裸鼠活体microPET显像,对荷肺腺癌裸鼠的瘤组织进行病理及氨肽酶N(APN)的免疫组织化学分析.采用两样本t检验分析数据.结果 68 Ga-DOTA-cNGR标记率为(99.8±0.1)％,性状稳定,在人血清中37℃保温2h后放化纯仍＞95％.正常小鼠体内生物分布结果表明,68Ga-DOTA-cNGR主要经肾排泄,血液清除迅速,肝、胃肠道摄取较少;1h肾、血液、肝、胃、肠的放射性摄取分别为(1.61±0.22)、(0.19±0.07)、(0.25±0.24)、(0.16±0.04)、(0.12±0.05) ％ID/g.荷肺腺癌裸鼠microPET显像可见肿瘤部位有放射性浓聚影,1h肿瘤与对侧正常肌肉T/NT高达7.61±0.47,经DOTA-cNGR特异性阻断后降至1.83±0.25,阻断前后差异有统计学意义(t=18.80,P＜0.05).免疫组织化学检查证实APN特异性聚集于肿瘤新生血管表面.结论 68 Ga-DOTA-cNGR易于制备,标记率和放化纯高,在人血清中的稳定性好,具有良好的代谢及肺腺瘤靶向特性,有望用于肺癌显像.
목적 제비68 Ga-1,4,7,10-사담잡배십이완-1,4,7,10-사을산-배상NGR(DOTA-cNGR),병평개기재정상소서체내적생물분포급대하폐선암라서적파향현상능력.방법 이간을기고진을류광산(HEPES)위완충체계(pH치5.0),수욕합성68Ga-DOTA-cNGR,HPLC측정표기솔급방화순,관찰기재인혈청중적은정성.진행68 Ga-DOTA-cNGR적정상소서체내생물분포화하폐선암라서활체microPET현상,대하폐선암라서적류조직진행병리급안태매N(APN)적면역조직화학분석.채용량양본t검험분석수거.결과 68 Ga-DOTA-cNGR표기솔위(99.8±0.1)％,성상은정,재인혈청중37℃보온2h후방화순잉＞95％.정상소서체내생물분포결과표명,68Ga-DOTA-cNGR주요경신배설,혈액청제신속,간、위장도섭취교소;1h신、혈액、간、위、장적방사성섭취분별위(1.61±0.22)、(0.19±0.07)、(0.25±0.24)、(0.16±0.04)、(0.12±0.05) ％ID/g.하폐선암라서microPET현상가견종류부위유방사성농취영,1h종류여대측정상기육T/NT고체7.61±0.47,경DOTA-cNGR특이성조단후강지1.83±0.25,조단전후차이유통계학의의(t=18.80,P＜0.05).면역조직화학검사증실APN특이성취집우종류신생혈관표면.결론 68 Ga-DOTA-cNGR역우제비,표기솔화방화순고,재인혈청중적은정성호,구유량호적대사급폐선류파향특성,유망용우폐암현상.
Objective To prepare 68Ga-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetroaceticacidcyclo NGD (DOTA-cNGR) and evaluate its biodistribution in normal mice and imaging efficacy in nude mice bearing human lung cancer.Methods 68Ga-DOTA-cNGR was synthesized through water bath at pH =5.0 with hydroxyl ethyl piperazine ethane sulfonic acid (HEPES) as the buffer system.The radiolabeling yield and radiochemistry purity were analyzed with HPLC.The stability of 68Ga-DOTA-cNGR in serum was measured.The biodistribution of 68Ga-DOTA-cNGR was studied in the normal mice (expressed as ％ID/g of tissues) and the nude mice bearing human lung cancer xenografts were imaged in vivo by microPET.Pathological and immunohistochemical analyses were performed on tumor tissues.Two-sample t test was used to analyze the data.Results The radiolabeling yield was (99.8±0.1)％ and radiochemical purity after 2 h in serum was more than 95％.Biodistribution study showed rapid clearance of 68Ga-DOTA-cNGR from the blood,and excretion was mainly via kidney with little uptake in the liver and gastrointestinal tract.The tracer uptake in kidneys,blood,liver,stomach,and intestine was (1.61 ± 0.22),(0.19 ± 0.07),(0.25 ± 0.24),(0.16±0.04),(0.12±0.05) ％ID/g respectively at 1 h post injection.The tumor uptake was significantly elevated on microPET with maximum T/NT of 7.61±0.47 at 1 h post injection.After specific blockage by DOTA-cNGR,the T/NT was significantly reduced to 1.83±0.25 (t=18.80,P＜0.05).The expression of aminopeptidase N was detected by immunohistochemistry.Conclusion 68 Ga-DOTA-cNGR could be successfully prepared with high radiolabeling yield and radiochemical purity.Its good stability in serum,ideal biodistribution and imaging characteristics are factors favoring the potential for imaging human lung cancer with over-expression of NGR receptors.