靶向磁性纳米粒子诊断胰腺癌活体MRI研究

Pancreatic Carcinoma in Nude Mice:Monoclonal Antibody Conjugated Superparamagnetic Iron Oxide Enhanced MR Imaging

目的:研究螯合单克隆抗体的超顺磁性氧化铁诊断胰腺癌荷瘤裸小鼠的可行性和价值。方法:胰腺癌荷瘤裸小鼠分为三组,每组6只。分别经尾静脉注射生理盐水、超顺磁性氧化铁、单克隆抗体的超顺磁性氧化铁粒子,行MRI检查,计算MRIT2WI信号下降程度。同时肿瘤组织病理切片行HE染色和普鲁士蓝染色,以及VEGF免疫组化检测,分析MRI强化形式和肿瘤组织病理HE染色、Fe染色以及VEGF表达之间的关系。结果:注射螯合单克隆抗体的超顺磁性氧化铁的裸小鼠肿瘤MRIT2WI信号下降比无抗体螯合组明显。普鲁士蓝染色显示氧化铁纳米粒子多数分布在肿瘤细胞核内。肿瘤细胞凋亡区的蓝色铁颗粒分布多于肿瘤细胞高密度区,而在完全坏死无结构区几乎没有蓝色铁颗粒显示。氧化铁纳米粒子在肿瘤内分布和肿瘤组织的VEGF高表达相一致。结论:螯合单克隆抗体的超顺磁性氧化铁可作为荷瘤裸小鼠胰腺癌MRI靶向对比剂。氧化铁纳米粒子在肿瘤内分布和肿瘤组织的血管通透性以及肿瘤细胞凋亡相关。

Purpose： To valuate monoclonal antibody （McAb） conjugated superparamagnetic iron oxide （SPIO） enhanced MR imaging on pancreatic carcinoma in nude mice. Methods： SPIO and McAb- SPIO were injected respectively into the nude mice with pancreatic carcinoma through the tail vein. All of the nude mice were performed MRI T2WI and FLASH T2WI scans after the injections. Hematoxylin and Eosin （HE） stain, Prussian blue stain and immunohistochemistry for VEGF were performed for the specimen of tumors. Results： A markedly MRI T2WI signal intensity decrease was observed in the tumor of McAb- SPIO - injected nude mice than in the SPIO - injected nude mice. The HE and Prussian blue stain showed that the amount of iron blue was higher in the area with apoptotic tumor cells than that with high density cells. The distribution of iron particles in tumor was consistent to the VEGF overexpression of tumor tissue. Conclusion： McAb - SPIO could be a tumor - targeted MR contrast agent for the diagnosis of pancreatic carcinoma in nude mice. The distribution of iron oxide in pancreatic carcinoma was in relation to VEGF overexpression and in the apoptosis of tumor cell.