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
2013年
4期
284-288
,共5页
涂少华%沈江帆%陶嵘%季晓雯%王雁程
塗少華%瀋江帆%陶嶸%季曉雯%王雁程
도소화%침강범%도영%계효문%왕안정
前列腺肿瘤%肿瘤移植%抗体,单克隆%放射性核素显像%小鼠,裸
前列腺腫瘤%腫瘤移植%抗體,單剋隆%放射性覈素顯像%小鼠,裸
전렬선종류%종류이식%항체,단극륭%방사성핵소현상%소서,라
Prostatic neoplasms%Neoplasm transplantation%Antibodies,monoclonal%Radionuclide imaging%Mice,nude
目的 研究99Tcm-抗前列腺特异性膜抗原(PSMA)抗体J591与前列腺癌细胞体外结合性能、在荷人前列腺癌裸鼠显像及体内分布情况.方法 用改进的Schwarz方法进行99Tcm标记J591,经Sephadex G-50柱分离纯化；用纸层析法和三氯醋酸法测定标记率与放化纯；用流式细胞术测定99Tcm-J591与肿瘤细胞在体外的结合性能.以PSMA阳性的C4-2前列腺癌荷瘤裸鼠为实验组,PSMA阴性的PC3前列腺癌荷瘤裸鼠为对照组,2组均经静脉注射99Tcm-J591 6.2～ 8.5 MBq(25 μg/只)后,分别于2、6、12及24h后行γ显像,利用ROI技术获得各时间点T/NT(NT为对侧肌肉组织).12 h显像后分批处死裸鼠(实验组4只,对照组5只),取肿瘤、心、肝、肾、胃、骨骼、肌肉和血液等组织,测湿质量和放射性计数,计算％ID/g,采用两样本t检验比较2组间差异.结果 99Tcm直接标记J591的标记率为(78.9±6.2)％,放化纯为(92.3±5.1)％,放射性比活度为68.7 MBq/mg.流式细胞术分析结果显示,J591与99Tcm-J591在体外均能结合PSMA阳性的C4-2细胞,与PSMA阴性的PC3细胞不结合.实验组静脉注射99Tcm-J591后6h,肿瘤部位出现明显放射性浓聚,至12 h放射性浓聚范围增大,边缘更清晰,2、6、12和24 h T/NT分别为1.9±1.1、4.3±1.8、5.6±2.7和1.4±0.6；对照组肿瘤部位未见明显放射性浓聚,各时间点T/NT均小于2.体内分布结果显示:注药后12 h,实验组肿瘤放射性为(20.1±5.2) ％ID/g,对照组为(5.8±2.6)％ID/g,两者差异有统计学意义(t=5.37,P＜0.001)；其余部位2组间放射性摄取差异无统计学意义(均t＜1.98,均P＞0.05).结论 99Tcm-J591具有良好的免疫活性和生物分布特性,对接种于裸鼠体内的人前列腺癌具有靶向定位性能,可望用于前列腺癌的导向诊断及导向治疗.
目的 研究99Tcm-抗前列腺特異性膜抗原(PSMA)抗體J591與前列腺癌細胞體外結閤性能、在荷人前列腺癌裸鼠顯像及體內分佈情況.方法 用改進的Schwarz方法進行99Tcm標記J591,經Sephadex G-50柱分離純化；用紙層析法和三氯醋痠法測定標記率與放化純；用流式細胞術測定99Tcm-J591與腫瘤細胞在體外的結閤性能.以PSMA暘性的C4-2前列腺癌荷瘤裸鼠為實驗組,PSMA陰性的PC3前列腺癌荷瘤裸鼠為對照組,2組均經靜脈註射99Tcm-J591 6.2～ 8.5 MBq(25 μg/隻)後,分彆于2、6、12及24h後行γ顯像,利用ROI技術穫得各時間點T/NT(NT為對側肌肉組織).12 h顯像後分批處死裸鼠(實驗組4隻,對照組5隻),取腫瘤、心、肝、腎、胃、骨骼、肌肉和血液等組織,測濕質量和放射性計數,計算％ID/g,採用兩樣本t檢驗比較2組間差異.結果 99Tcm直接標記J591的標記率為(78.9±6.2)％,放化純為(92.3±5.1)％,放射性比活度為68.7 MBq/mg.流式細胞術分析結果顯示,J591與99Tcm-J591在體外均能結閤PSMA暘性的C4-2細胞,與PSMA陰性的PC3細胞不結閤.實驗組靜脈註射99Tcm-J591後6h,腫瘤部位齣現明顯放射性濃聚,至12 h放射性濃聚範圍增大,邊緣更清晰,2、6、12和24 h T/NT分彆為1.9±1.1、4.3±1.8、5.6±2.7和1.4±0.6；對照組腫瘤部位未見明顯放射性濃聚,各時間點T/NT均小于2.體內分佈結果顯示:註藥後12 h,實驗組腫瘤放射性為(20.1±5.2) ％ID/g,對照組為(5.8±2.6)％ID/g,兩者差異有統計學意義(t=5.37,P＜0.001)；其餘部位2組間放射性攝取差異無統計學意義(均t＜1.98,均P＞0.05).結論 99Tcm-J591具有良好的免疫活性和生物分佈特性,對接種于裸鼠體內的人前列腺癌具有靶嚮定位性能,可望用于前列腺癌的導嚮診斷及導嚮治療.
목적 연구99Tcm-항전렬선특이성막항원(PSMA)항체J591여전렬선암세포체외결합성능、재하인전렬선암라서현상급체내분포정황.방법 용개진적Schwarz방법진행99Tcm표기J591,경Sephadex G-50주분리순화；용지층석법화삼록작산법측정표기솔여방화순；용류식세포술측정99Tcm-J591여종류세포재체외적결합성능.이PSMA양성적C4-2전렬선암하류라서위실험조,PSMA음성적PC3전렬선암하류라서위대조조,2조균경정맥주사99Tcm-J591 6.2～ 8.5 MBq(25 μg/지)후,분별우2、6、12급24h후행γ현상,이용ROI기술획득각시간점T/NT(NT위대측기육조직).12 h현상후분비처사라서(실험조4지,대조조5지),취종류、심、간、신、위、골격、기육화혈액등조직,측습질량화방사성계수,계산％ID/g,채용량양본t검험비교2조간차이.결과 99Tcm직접표기J591적표기솔위(78.9±6.2)％,방화순위(92.3±5.1)％,방사성비활도위68.7 MBq/mg.류식세포술분석결과현시,J591여99Tcm-J591재체외균능결합PSMA양성적C4-2세포,여PSMA음성적PC3세포불결합.실험조정맥주사99Tcm-J591후6h,종류부위출현명현방사성농취,지12 h방사성농취범위증대,변연경청석,2、6、12화24 h T/NT분별위1.9±1.1、4.3±1.8、5.6±2.7화1.4±0.6；대조조종류부위미견명현방사성농취,각시간점T/NT균소우2.체내분포결과현시:주약후12 h,실험조종류방사성위(20.1±5.2) ％ID/g,대조조위(5.8±2.6)％ID/g,량자차이유통계학의의(t=5.37,P＜0.001)；기여부위2조간방사성섭취차이무통계학의의(균t＜1.98,균P＞0.05).결론 99Tcm-J591구유량호적면역활성화생물분포특성,대접충우라서체내적인전렬선암구유파향정위성능,가망용우전렬선암적도향진단급도향치료.
Objective To study the binding performance of 99Tcm labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody J591 (99Tcm-J591) and prostate cancer cells in vitro,the biodistribution and SPECT imaging of 99Tcm-J591 in nude mice bearing human prostate cancer in vivo.Methods The monoclonal antibody J591 was labeled with 99Tcm by improved Schwarz method.Labeled antibody was purified by Sephadex G-50.The labeling efficiency and radiochemical purity were measured by paper chromatography and trichloroacetic acid method.The binding performance of J591 and prostate cancer cells was measured by flow cytometry in vitro.The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts served as experiment group,mice bearing PSMA-negative PC3 tumors served as control group.6.2-8.5 MBq of 99Tcm-J591 (25 μg) was intravenously injected into mice.Gamma imaging was performed 2,6,12 and 24 h after injection,T/NT was calculated by ROI technique.After scanned 12 h post injection,4 mice of the experiment group and 5 mice of the control group were sacrificed and the tracer in vivo biodistribution was measured by gamma-counting,and the ％ ID/g was calculated.Two-sample t test was carried out to validate significant difference of ％ID/g between two groups.Results The labeling efficiency and radiochemieal purity of 99Tcm-J591 were (78.9±6.2)％ and (92.3±5.1)％,respectively,and the specific activity of 99Tcm-J591 was 68.7 MBq/mg.The antibody J591 and 99Tcm-J591 could strongly combine with PSMA-positive C4-2 cells in vitro,and didn't combine with PSMA-negative PC3 cells in vitro.SPECT imaging results showed that radioactive concentration was obvious in tumor 6 h post injection,the concentration scope became large and the tumor image was clear 12 h post injection.T/NT was 1.9±1.1 at 2 h,4.3±1.8 at 6 h,5.6±2.7 at 12 h,1.4±0.6 at 24 h,respectively.In the control group,no radioactivity concentration was found in tumor,and T/NT was less than 2.The biodistribution results showed that ％ID/g of tumor tissue was 20.1±5.2 in the experiment group and 5.8±2.6 in the control group,and there was significant difference (t=5.37,P＜0.001).No significant tracer uptake occurred in other tissues and organs between the two groups (all t＜ 1.98,all P＞0.05).Conclusion The immunoactivity,characteristics of biodistribution and tumor targeting property of monoclonal antibody J591 show promising future and potential values in diagnosis and therapy of prostate cancer.
