摘要
目的了解131I标记的胃泌素释放肽前体（ProGRP）单克隆抗体E-B5在荷小细胞肺癌裸鼠的体内分布及放射免疫显像情况，观察131I—E—B5对荷小细胞肺癌裸鼠移植瘤的生长抑制作用。方法（1）分别建立荷小细胞肺癌、荷肺腺癌及荷大肠癌裸鼠模型。（2）自荷小细胞肺癌裸鼠尾静脉注射131I—E-B5后1，12，24，48，72和96h处死裸鼠并取各主要脏器组织，计算各时间点的每克组织百分注射剂量率（％ID／g）和肿瘤／非肿瘤放射性（T／NT）比值。（3）分别对荷小细胞肺癌、荷肺腺癌和荷大肠癌裸鼠模型进行131I—E—B5放射免疫显像，观察移植瘤的显影情况，并计算移植瘤体／对侧相同部位的放射性（T／B）比值。（4）以未经任何治疗处理组为对照，采用瘤内注射法观察比较3．7，7．4，14．8和22．2MBq131I-E—B5和Na131I对荷小细胞肺癌裸鼠移植瘤的抑制作用。采用SPSS13．0软件处理数据，行两样本均数t检验。结果（1）体内分布研究示：注射后72h，荷小细胞肺癌裸鼠移植瘤体的放射性摄取达到最高值，为（14．1±2．9）％ID／g，高于其他脏器及组织（t=4．11～8．58，P均〈0．05），瘤体与各脏器组织的T／NT比值随时间延长而逐渐升高，72h时瘤体与肌肉组织的T／NT比值高达4．67±0．66。（2）放射免疫显像发现：注射131I—E—B5后24h荷小细胞肺癌裸鼠移植瘤部位放射性明显聚集，随时间延长放射性浓聚程度逐渐增强，72至96h时最为清晰。荷肺腺癌裸鼠移植瘤局部无明显的放射性浓聚。荷大肠癌裸鼠移植瘤模型显像结果与荷小细胞肺癌裸鼠模型显像结果类似，但其T／B比值低于荷小细胞肺癌裸鼠模型（t=4．29，P〈0．01）。注射后72h，荷小细胞肺癌、荷大肠癌及荷肺腺癌裸鼠的T／B比值分别为5．27±0．97，2．28±0．72和1．26±0．65。（3）131I—E-B5对荷小细胞肺癌移植瘤的生长抑制作用明显大于Na131I（t=2．88～17．77，P均〈0．05）。结论131I—E—B5对小细胞肺癌有较好的靶向作用，可以抑制小细胞肺癌移植的生长并破坏肿瘤组织，有望成为一种较为理想的小细胞肺癌放射免疫显像及放射免疫治疗药物，值得进一步深入研究。
Objective To explore the biodistribution, radioimmunoimaging and anti-tumor effect of 131I labeling anti-progastrin-releasing peptide（31-98） （ ProGRP（31-98） ） monoclonal antibody E-B5 （ 131I-E-B5 ） in nude mice bearing human small cell lung cancer （SCLC）. Methods Nude mice bearing human SCLC were sacrificed at 1, 12, 24, 48, 72 and 96 h after injection with 131I-E-B5 through tail vein. Their organs were harvested for calculating percentage activity of injection dose per gram of tissue （ % ID/g） and the radioactivity ratio of tumor/non-tumor （T/NT）. Continuous images of the nude mice bearing SCLC, lung adenocareinoma and colon cancer were carried out respectively at 1,4, 8, 10, 24, 48, 72 and 96 h after injection of 131I-E-B5 Transplantation tumor images were then observed and the radioactivity ratio of tumor/background （T/B） was calculated. The nude mice bearing SCLC were divided into 3 groups, including 131I-E-B5 , Na131 I and control groups. From the flint to the fourth week after intratumoral injections, the tumor sizes were measured and compared. Continuous variables were expressed as x ＋ s and compared by t-test with SPSS 13.0software. Results （1） The peak uptake of131I-E-B5 in xenograft tumor of SCLC was at 72 h after injection （ （ 14.1 ±2.9 ） % ID/g） with a T/B ratio of 4.67 ＋ 0.66. （ 2 ） Accumulation of 131I-E-B5 atxenograft tumor of SCLC was visualized at 24 h with highest T/B ratio at 72 h to 96 h post-injection. At 72 h after injection, the T/B ratio of xenograft tumor of SCLC, colon cancer and lung adenocarcinoma was 5.27 ±0O. 97, 2.28 ± 0.72 and 1.26 ± 0.65, respectively and was consistent with the biodistribution in nude mice bearing SCLC. （3） The inhibition ratio of SCLC of the 131I-E-B5 group was conspicuous higher than that of Na131 I group （ t= 2.88 to 17.77, all P 〈 0.05 ）. Conclusion 131I-E-B5 could effectively target SCLC and inhibit the growth of tumor, therefore was a promising radioimmunoimaging and radioimmunotherapy radiopharmaceutical for SCLC.
出处
《中华核医学杂志》
CAS
CSCD
北大核心
2010年第2期110-115,共6页
Chinese Journal of Nuclear Medicine
基金
基金项目：苏州市科技发展计划应用基础研究（医疗卫生）项目（YJS0926）
关键词
小细胞肺癌
抗体
单克隆
胃泌素释放肽
放射性核素显像
放射免疫疗法
小鼠
裸
Small cell lung carcinoma
Antibodies, monoclonal
Gastrin-releasing peptide
Radionuclide imaging
Radioimmunotherapy
Mice, Nude
