^125I标记聚酰胺-胺及其在小鼠体内的生物分布  

Labeling of polyamidoamine with ^125I and its biodistribution in mice

作　　者：刘鉴峰[1] 刘金剑[1] 褚丽萍[1] 王德芝[1] 贺欣[1] 徐宏艳[1] 

机构地区：[1]中国医学科学院放射医学研究所,天津市分子核医学重点实验室,天津300192

出　　处：《国际放射医学核医学杂志》2013年第2期65-68,共4页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金（81171371、30700178、51203189）：天津市自然科学基金（09JCYBJC13400）;中国医学科学院放射医学研究所学科发展基金（SF1209）

摘　　要：目的研究^125I标记的树枝状高分子纳米材料聚酰胺-胺（PAMAM）在小鼠体内的生物分布。方法通过羟基琥珀酰亚胺将酪氨酸连接到4代PAMAM上，再对PAMAM进行mI标记，透析法对标记化合物进行纯化，放射性薄层扫描对标记物进行标记率、放化纯度及稳定性检测。将^125I-PAMAM经尾静脉注射入小鼠体内，分别在1、4、8、24、48h时对小鼠进行活体成像，并取主要脏器进行放射性计数。结果磁共振氢谱法检测结果显示，每个PAMAM分子上约连接了两个酪氨酸分子，标记率约为56％，放化纯度〉98％，标记化合物具有良好的稳定性，体外放置72h放化纯度仍〉90％。小动物活体成像结果显示，PAMAM主要聚集在肝脏部位。各组织的放射性计数与显像结果基本一致，主要分布在肝、肾和脾中，而且体内代谢较慢，48h时在小鼠体内仍有较高分布。结论未经修饰的PAMAM在肝、肾及脾中大量聚集，体内代谢缓慢，不适合直接作为药物载体进行使用，需进行化学修饰来加速体内代谢，防止体内蓄积从而引起不良反应。Objective To investigate the biodistribution of ^125I labeled dendrimer nanomaterial-- polyamidoamine （PAMAM） in mice. Methods Tyrosine was conjugated to four generation PAMAM by N- Hydroxysuecinimide, then ^125I was labeled on PAMAM with chloramines-T method, and purified by dialysis. Labeling rate, radiochemical purity and stability of ^125I-PAMAM were detected by radioactive thin layer chromatography scanning. The gamma imaging and biodistribution were detected by in vivo imaging system and gamma counter at one, four, eight, twenty-four and forty-eight hours after intravenous injection. Results The ^1H nuclear magnetic resonance results showed that about two tyrosines were conjugated to PAMAM. The ^125I labeling rate was about 56% and radiochemical purity was more than 98%. The radiochemical purity of labeled compound remained more than 90% at 72 hours in vitro. In vivo imaging results showed that PAMAM was mainly accumulated in liver periphery. The gamma counter results showed that PAMAM mainly accumulated in liver, kidney and spleen, the excretion of PAMAM was slow and there has high dose of PAMAM in mice at 48 hours. Conclusion PAMAM with no chemical modification was mainly accumulated in liver, kidney and spleen, and the excretion of PAMAM was slow, so PAMAM is not fit as drug carrier. PAMAM need to chemical modification to accelerate excretion and prevent the emergence of toxicity caused by accumulation in body.

关 键 词：碘放射性同位素 聚酰胺-胺 体内分布 

分 类 号：R9[医药卫生—药学]