摘要
目的:开发一种具有"找寻、治疗、可视"功能的生物造影剂。方法:采用化学合成的方法得到近红外标记的维甲酸类造影剂,并进行骨肉瘤细胞的体外结合试验;皮下接种裸鼠,构建骨肉瘤的异种移植模型,持续10d对裸鼠进行体内光学成像,观察药物在体内的重新分布,并最终用免疫组织化学法对成像结果进行验证。结果:体外细胞结合试验证明,合成的维甲酸造影剂可以很好的与人的骨肉瘤细胞相结合,进而内化。近红外光学成像表明,该造影剂可用于骨肉瘤的早期和晚期诊断。全身成像显示了在肿瘤和肝脏的高信号强度。正电子发射断层显像(PET)显示肿瘤部位具有较高水平的18F-FDG代谢。剂量增加反应和毒性试验表明,高剂量的维甲酸造影剂必然与其全身毒性息息相关。免疫组化染色显示,发光组织中肿瘤细胞呈阳性。结论:合成的近红外标记的维甲酸造影剂可以用于检测人类骨肿瘤的异种移植,实现个体化分子诊疗的同时减少全身毒性。
Objective: To develop a kind of biological contrast agent with the features of "finding,treatment,visual".Methods: Retinoid imaging agents are synthesized and labeled with near-infrared dye for in vitro cell binding studies on human osteosarcoma cell lines.Xenograft model was establish by subcutaneous injection(s.c.);In vivo optical imaging studies were carried out for days after injection,drug redistribution in the body was detected.Tumor cells in the luminous tissue wre detected by immunochemistry.Results: Those agents bound to the human osteosarcoma cells,and internalized,which can be used to detect osteosarcoma at early stages of the metastatic disease.Whole body images showed the high signal intensity in tumor and liver.PET showed that there was high level of 18F-FDG in tumors.The high dose of retinoid agent was significantly associated with systemic toxcity.Immunochemistry demonstrated tumor cells were positive in the luminous tissues.Conclusion: Synthetic NIR-labeled retinoid agents can be used to detect human cancer xenografts as the agent is internalized by cancer cells,and it can reduce systemic toxicity.
出处
《现代生物医学进展》
CAS
2011年第8期1424-1427,共4页
Progress in Modern Biomedicine
基金
国家自然科学基金面上项目(30873027
30973409)
关键词
分子成像
细胞摄取
光学成像
肿瘤
近红外
Molecular imaging
Cellular uptake
Optical imaging
Cancer
Near-infrared