^99Tc^m-J591的制备及荷人前列腺癌裸鼠显像  

The preparation of ^99Tc^m-J591 and its SPECT imaging of nude mice bearing human prostate cancer

作　　者：涂少华[1] 沈江帆[1] 陶嵘[1] 季晓雯[1] 王雁程[1] 

机构地区：[1]上海中医药大学附属普陀医院核医学科,200062

出　　处：《中华核医学与分子影像杂志》2013年第4期284-288,共5页Chinese Journal of Nuclear Medicine and Molecular Imaging

摘　　要：目的研究^99Tc^m-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^99Tc^m标记J591，经SephadexG-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^99Tc^m-J591与肿瘤细胞在体外的结合陛能。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^99Tc^m-J5916．2—8．5MBq（25μg／只）后，分别于2、6、12及24h后行1显像，利用ROI技术获得各时间点T／NT（NT为对侧肌肉组织）。12h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￡检验比较2组间差异。结果”Tc。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68．7MBq／mg。流式细胞术分析结果显示，J591与^99Tc^m-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”Tcm-J591后6h，肿瘤部位出现明显放射性浓聚，至12h放射性浓聚范围增大，边缘更清晰，2、6、12和24hT／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12h，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c〈1．98，均P〉0．05）。结论^99Tc^m-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。Objective To study the binding performance of ^99Tc^m labeled anti-human prostatic spe- cific membrane antigen （PSMA） monoclonal antibody J591 （99Tern-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 anti- body was purified by Sephadex G-50. The labeling efficiency and radioehemical purity were measured by pa- per 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 carcino- ma xenografts served as experiment group, mice bearing PSMA-negative PC3 tumors served as control group. 6.2-8.5 MBq of 99Tern-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 injec- tion, 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 radiochemical purity of 99Tcm-J591 were （78.9±6.2）% and （92.3±5.1）%, respectively, and the spe- cific activity of 99Tern-J591 was 68.7 MBq/mg. The antibody J591 and 99Tern-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 concentra- tion 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 concentra- tion was found in tumor, and T/NT was less

关 键 词：前列腺肿瘤 肿瘤移植 抗体 单克隆 放射性核素显像 小鼠 裸 

分 类 号：R737.25[医药卫生—肿瘤]