摘要
背景与目的:基质金属蛋白酶(matrixmetalloproteinases,MMPs)在肿瘤生长和转移的多个环节发挥着重要作用,Ⅳ型胶原酶作为MMPs家族的重要成员之一已成为肿瘤研究的新靶点。本文通过荷瘤裸鼠的显像实验,评价抗Ⅳ型胶原酶单克隆抗体3G11的体内特异性分布。方法:用Iodogen法将131I或125I标记亲和纯化的单抗3G11,ELISA检测标记前后单抗的活性变化。131I-3G11在3种不同体系(生理盐水,小牛血清,裸鼠血清)中37℃温育,检测体外稳定性。每只正常BALB/c小鼠静脉注入388.5kBq125I-3G11,测定单抗的药动学指标。建立人高转移PG肺癌细胞移植肿瘤模型的BALB/c(nu/nu)裸鼠每只静脉注入6.44MBq131I-3G11,进行免疫显像。结果:单抗3G11经亲和纯化后纯度大于98%,碘标记使单抗活性降低10%～20%。单抗3G11的体内代谢呈二室模型分布,T1/2α为7.2h,T1/2β为345.2h。131I-3G11标记物体外72h能基本保持稳定,在荷瘤裸鼠体内72h显像清晰,至120h效果更明显。结论:显像实验证明单抗3G11对肿瘤组织有较好的特异性和亲和性。
BACKGROUND &OBJECTIVE:Matrix metalloproteinases (MMPs)play the im portant role in many steps of tumor growth and metastasis. Type Ⅳcollagenase, w hich is a key member of MMPs family, has been viewed as a promising target in tu mor study. The aim of this study was to evaluate the tumor-specific distributio n of the anti-type Ⅳcollagenase monoclonal antibody (mAb) 3G11 by radioimaging in tumor-bearing nude mice. METHODS: MAb 3G11 purified by affinity chromatogra phy was labeled with either 131-or 125-iodide by the Iodogen method. Immunorea ctivity of mAb 3G11 was determined by ELISA. 131I-labeled 3G11 was incubated in three different media at 37℃and its in vitro stability was tested. Normal BALB /c mice were injected intravenously with 388.5 kBq per mouse of 125I-labeled 3G 11 to explore the pharmacokinetic patterns. The scintigraphic images of human lu ng carcinoma PG xenografts grown subcutaneously in BALB/c nude mice were made af ter intravenously administrating of 6.44 MBq per mouse of 131I-labeled 3G11. RE SULTS: MAb 3G11 was more than 98%in purity via affinity purification. The immun oreactivity of mAb 3G11 decreased by approximately 10%-20%after cold iodinati on. Patterns of blood clearance of mAb 3G11 was defined as two-compartment mode l, with T1/2αand T1/2βcalculated to be 7.2 h and 345.2 h, respectively. 131I- labeled 3G11 was almost stable in vitro for 72 h. A clear image of the xenograft ed tumor was obtained at 72 h, and it further improved at 120 h. CONCLUSION: MAb 3G11 showed high specificity and affinity with tumor tissue through scintiscann ing.
出处
《癌症》
SCIE
CAS
CSCD
北大核心
2003年第12期1243-1248,共6页
Chinese Journal of Cancer
基金
国家重点基础性研究973项目基金(No.G1998051212)
关键词
抗Ⅳ型胶原酶
肺癌
移植模型
免疫显像
单克隆抗体
碘同位素
Type Ⅳcollagenase
Monoclonal antibody
Iodine isotope
Immunoscint igraphy
Lung Cancer xenograft
