中华核医学与分子影像杂志
中華覈醫學與分子影像雜誌
중화핵의학여분자영상잡지
Chinese Journal of Nuclear Medicine and Molecular Imaging
2015年
5期
359-363
,共5页
谢亦驰%周小林%郝丽君%洪智慧%沈明敬%徐忠恒%石怡珍%刘增礼
謝亦馳%週小林%郝麗君%洪智慧%瀋明敬%徐忠恆%石怡珍%劉增禮
사역치%주소림%학려군%홍지혜%침명경%서충항%석이진%류증례
癌,小细胞%肺%抗体,单克隆%胃泌素释放肽%放射性核素显像%小鼠,裸
癌,小細胞%肺%抗體,單剋隆%胃泌素釋放肽%放射性覈素顯像%小鼠,裸
암,소세포%폐%항체,단극륭%위비소석방태%방사성핵소현상%소서,라
Carcinoma,small cell%Lung%Antibodies,monoclonal%Gastrin-releasing peptide%Radionuclide imaging%Mice,nude
目的 研究99Tcm标记的抗胃泌素释放肽前体[ProGRP(31-98)]单克隆抗体D-D3在荷人小细胞肺癌(SC LC)裸鼠体内的生物分布及放射免疫显像情况.方法 (1)采用2-巯基乙醇还原法制备99Tcm-D-D3,凝胶柱分离法纯化标记产物,纸层析法检测标记率、放化纯、比活度及稳定性,细胞结合分析法测定标记抗体的抗原结合能力.(2)建立SCLC NCI-H446及肺腺癌A549荷瘤裸鼠模型.(3)自NCl-H446荷瘤裸鼠尾静脉注射99Tcm-D-D3后,于不同时间点处死裸鼠并取血液及各主要脏器组织标本,计算各时间点的放射性摄取值(％ID/g)和肿瘤/肌肉、肿瘤/血液的放射性计数比值.(4)对荷瘤裸鼠模型进行放射免疫显像,计算T/NT比值.采用SPSS 17.0软件处理数据,两样本均数比较采用两样本t检验.结果 (1) 99Tcm-D-D3标记率为(73.87±2.89)％,放化纯为(94.13±4.49)％,比活度为(1.64±0.06) MBq/μg.与生理盐水及健康人血清充分混合,37℃放置4h后的放化纯分别为(82.17±1.00)％和(74.13±1.67)％,12 h后的放化纯分别为(55.73±1.07)％和(54.07±1.88)％.99 Tcm-D-D3与NCI-H446和A549细胞结合率分别为(81.20±2.37)％和(24.30± 1.46)％.(2) NCI-H446荷瘤裸鼠体内生物分布研究显示:注射99Tcm-D-D3后8h,瘤体的放射性摄取值[(2.13±0.06) ％ID/g]已明显高于除肝、肾、胃及血液外的其他脏器及组织(t=2.52～ 24.53,均P＜0.05),12h时显著高于其他脏器及组织(t=1.98～20.88,均P＜0.05),24 h时达最高值[(4.16±0.45) ％ID/g];肿瘤/肌肉、肿瘤/血液的放射性比值随时间延长而逐渐升高.(3)放射免疫显像结果显示:注射后4h,NCI-H446荷瘤裸鼠的瘤体已较清晰,随时间延长移植瘤部位的放射性逐渐增多.A549荷瘤裸鼠注射99Tcm-D-D3后24 h内,移植瘤局部仅见少量放射性聚集,隐约可见移植瘤轮廓,其放射性聚集程度与周围组织的差异甚小.结论 99Tcm-D-D3能选择性聚集在NCI-H446移植瘤部位,具有潜在的SCLC靶向功能.
目的 研究99Tcm標記的抗胃泌素釋放肽前體[ProGRP(31-98)]單剋隆抗體D-D3在荷人小細胞肺癌(SC LC)裸鼠體內的生物分佈及放射免疫顯像情況.方法 (1)採用2-巰基乙醇還原法製備99Tcm-D-D3,凝膠柱分離法純化標記產物,紙層析法檢測標記率、放化純、比活度及穩定性,細胞結閤分析法測定標記抗體的抗原結閤能力.(2)建立SCLC NCI-H446及肺腺癌A549荷瘤裸鼠模型.(3)自NCl-H446荷瘤裸鼠尾靜脈註射99Tcm-D-D3後,于不同時間點處死裸鼠併取血液及各主要髒器組織標本,計算各時間點的放射性攝取值(％ID/g)和腫瘤/肌肉、腫瘤/血液的放射性計數比值.(4)對荷瘤裸鼠模型進行放射免疫顯像,計算T/NT比值.採用SPSS 17.0軟件處理數據,兩樣本均數比較採用兩樣本t檢驗.結果 (1) 99Tcm-D-D3標記率為(73.87±2.89)％,放化純為(94.13±4.49)％,比活度為(1.64±0.06) MBq/μg.與生理鹽水及健康人血清充分混閤,37℃放置4h後的放化純分彆為(82.17±1.00)％和(74.13±1.67)％,12 h後的放化純分彆為(55.73±1.07)％和(54.07±1.88)％.99 Tcm-D-D3與NCI-H446和A549細胞結閤率分彆為(81.20±2.37)％和(24.30± 1.46)％.(2) NCI-H446荷瘤裸鼠體內生物分佈研究顯示:註射99Tcm-D-D3後8h,瘤體的放射性攝取值[(2.13±0.06) ％ID/g]已明顯高于除肝、腎、胃及血液外的其他髒器及組織(t=2.52～ 24.53,均P＜0.05),12h時顯著高于其他髒器及組織(t=1.98～20.88,均P＜0.05),24 h時達最高值[(4.16±0.45) ％ID/g];腫瘤/肌肉、腫瘤/血液的放射性比值隨時間延長而逐漸升高.(3)放射免疫顯像結果顯示:註射後4h,NCI-H446荷瘤裸鼠的瘤體已較清晰,隨時間延長移植瘤部位的放射性逐漸增多.A549荷瘤裸鼠註射99Tcm-D-D3後24 h內,移植瘤跼部僅見少量放射性聚集,隱約可見移植瘤輪廓,其放射性聚集程度與週圍組織的差異甚小.結論 99Tcm-D-D3能選擇性聚集在NCI-H446移植瘤部位,具有潛在的SCLC靶嚮功能.
목적 연구99Tcm표기적항위비소석방태전체[ProGRP(31-98)]단극륭항체D-D3재하인소세포폐암(SC LC)라서체내적생물분포급방사면역현상정황.방법 (1)채용2-구기을순환원법제비99Tcm-D-D3,응효주분리법순화표기산물,지층석법검측표기솔、방화순、비활도급은정성,세포결합분석법측정표기항체적항원결합능력.(2)건립SCLC NCI-H446급폐선암A549하류라서모형.(3)자NCl-H446하류라서미정맥주사99Tcm-D-D3후,우불동시간점처사라서병취혈액급각주요장기조직표본,계산각시간점적방사성섭취치(％ID/g)화종류/기육、종류/혈액적방사성계수비치.(4)대하류라서모형진행방사면역현상,계산T/NT비치.채용SPSS 17.0연건처리수거,량양본균수비교채용량양본t검험.결과 (1) 99Tcm-D-D3표기솔위(73.87±2.89)％,방화순위(94.13±4.49)％,비활도위(1.64±0.06) MBq/μg.여생리염수급건강인혈청충분혼합,37℃방치4h후적방화순분별위(82.17±1.00)％화(74.13±1.67)％,12 h후적방화순분별위(55.73±1.07)％화(54.07±1.88)％.99 Tcm-D-D3여NCI-H446화A549세포결합솔분별위(81.20±2.37)％화(24.30± 1.46)％.(2) NCI-H446하류라서체내생물분포연구현시:주사99Tcm-D-D3후8h,류체적방사성섭취치[(2.13±0.06) ％ID/g]이명현고우제간、신、위급혈액외적기타장기급조직(t=2.52～ 24.53,균P＜0.05),12h시현저고우기타장기급조직(t=1.98～20.88,균P＜0.05),24 h시체최고치[(4.16±0.45) ％ID/g];종류/기육、종류/혈액적방사성비치수시간연장이축점승고.(3)방사면역현상결과현시:주사후4h,NCI-H446하류라서적류체이교청석,수시간연장이식류부위적방사성축점증다.A549하류라서주사99Tcm-D-D3후24 h내,이식류국부부견소량방사성취집,은약가견이식류륜곽,기방사성취집정도여주위조직적차이심소.결론 99Tcm-D-D3능선택성취집재NCI-H446이식류부위,구유잠재적SCLC파향공능.
Objective To explore the biodistribution and radioimmunoimaging of 99Tcm-labeled anti-ProGRP monoclonal antibody D-D3 in nude mice bearing human small cell lung cancer (SCLC) xenografts.Methods (1) D-D3 antibody was labeled with 99Tcm via the 2-mercaptoethanol reduction method.99Tcm-D-D3 was purified by the gel column separation method.The labeling efficiency,radiochemical purity,specific radioactivity and stability of 99Tcm-D-D3 were measured by thin-layer chromatography.Antigen-binding ability was determined by cell binding assay.(2)After tail vein injection of 99Tcm-D-D3,nude mice bearing SCLC NCI-H446 xenografts were sacrificed at designated time points.The blood and major organs were removed and weighed,and counted in a gamma scintillation counter.Radioactive uptake in each organ (％ID/g),tumor/muscle and tumor/blood ratios at each time point were calculated.(3)After injection of 99Tcm-D-D3,continuous imaging of the nude mice bearing NCI-H446 and lung adenocarcinoma A549 xenografts were carried out respectively,and the T/NT ratios were calculated.Two-sample t test was used to analyze the data.Results (1) The labeling rate of 99Tcm-D-D3 was (73.87±2.89)％.The radiochemical purity was (94.13±4.49) ％.The specific radioactivity was (1.64±0.06) MBq/μg.Being fully mixed with either saline or healthy human serum and incubated at 37 ℃ for 4 h,the radiochemical purities of 99Tcm-D-D3 were (82.17± 1.00) ％ and (74.13±1.67) ％ respectively,and (55.73± 1.07) ％ and (54.07± 1.88) ％ respectively after being incubated for 12 h.The immunobinding rates of 99Tcm-D-D3 to NCI-H446 and A549 cells were (81.20± 2.37) ％ and (24.30± 1.46) ％,respectively.(2) The ％ID/g of 99Tcm-D-D3 in NCI-H446 tumor was 2.13± 0.06,which was significantly higher than those of other organs except liver,kidneys,stomach and blood at 8 h after injection (t =2.52-24.53,all P＜0.05).The uptake in the tumors was higher than those of all other organs at 12 h (t=1.98-20.88,all P＜0.05),and reached the peak level (4.16±0.45) ％ID/g at 24 h.The tmor/muscle and tumor/blood ratios gradually increased with time.(3) At 2 h after injection of 99Tcm-D-D3,the tumor in NCI-H446 bearing nude mice could be visualized and definitely delineated at 4 h.The tumor uptake of 99Tcm-D-D3 gradually increased.No significant accumulation of 99Tcm-D-D3 was found in the A549 tumor mass from 1 to 24 h after injection.Conclusion 99Tcm-D-D3 can selectively accumulate in the tumor site of NCI-H446 xenografts and has a potential targeting property to SCLC.
