^(99)Tc^m标记的新型糖基化生长抑素生物学评价  

Biological Properties Evaluation of a Novel Glycosylated Somatostatin Labeled With ^(99)Tc^m

作　　者：何川[1] 翟士桢[2] 杜进[1] 戴皓洁[3] 罗莎[3] 

机构地区：[1]中国原子能科学研究院同位素研究所,北京102413 [2]北京大学基础医学院生物物理系,北京100083 [3]首都医科大学附属北京同仁医院,北京100730

出　　处：《同位素》2007年第1期11-15,共5页Journal of Isotopes

基　　金：国家自然科学基金(30370421);教育部留学回国人员科研启动基金资助项目

摘　　要：以天然生长抑素(Somatostatin,SMS)、葡聚糖-10(Dextran10,Dx10)及双功能螯合剂硫代乙酰基-巯基乙酰-二甘氨酰-赖氨酸(MAG2Lys)为原料,合成了新型生长抑素配体化合物SMS-Dx10-MAG2Lys,并对其进行了99Tcm标记;以125I-奥曲肽(125I-Tyr3-Octreotide)为放射配基,进行受体竞争结合实验,测定SMS-Dx10-MAG2Lys的IC50值;并用99Tcm-MAG2Lys-Dx10-SMS进行正常SD大鼠体内分布、血浆清除以及肿瘤模型动物显像实验。结果表明:配体化合物SMS-Dx10-MAG2Lys保持了对生长抑素2型受体高亲和力,其IC50与SMS相近;99Tcm-MAG2Lys-Dx10-SMS在正常大鼠体内血浆半减期为2.4h,主要浓聚于肝、脾脏并经肾排泄,与葡聚糖的代谢途径基本一致;荷胰腺癌裸鼠显像表明,注射后4h,肿瘤组织具有明显的放射性摄取。以上结果表明,99Tcm-MAG2Lys-Dx10-SMS有望成为一种新型生长抑素受体阳性肿瘤显像剂。Natural somatostatin （SMS）, dextran-10 （Dx^10） and a new bifunctional chelator S-Acetyl-Mercaptoacetyl-glycyl-glycyl-Lysine （MAG2Lys） are used to synthesize a novel somatostatin-dextran-MAGz Lys （SMS-Dx^10-MAGz Lys） conjugate, then the conjugate is radiolabeled with ^99Tc^m. The value of IC50 of SMS-Dx^10-MAGz Lys is tested by in vitro somatostatin receptor competition binding study using ^125I-Tyr^3-Octreotide as a radioligand. The biodistribution and blood half-life of ^99 Tc^m-MAG2Lys-Dx^10-SMS are investigated in normal rats. The tumor uptake and imaging properties of ^99 Tc^m-MAG2 Lys-Dx^10-SMS are evaluated in nude mice bearing human pancreatic tumor. The SMS-Dx^10-MAG2Lys shows high somatostatin receptor binding affinity, in the same IC50 value range as the reference ligand somatostatin （IC50～1.0 nmol/L）. The blood half-life of ^99Tc^m-MAG2Lys-Dx^10-SMS is 2.4 h post injection in normal rats. The excretion is mainly through the hepatobiliary and kidney system. The ^99Tc^m-MAG2Lys-Dx^10-SMS is localized in pancreatic tumor and shows visible tumor uptake at 4 h imaging. The results indicate that ^99Tc^m-MAG2 Lys-Dx^l0-SMS is a novel and potential imaging agent for Somatostatin receptor positive tumor.

关 键 词：^99TC^M 葡聚糖 生长抑素 血液半衰期 肿瘤 

分 类 号：R817.1[医药卫生—影像医学与核医学] O628.51[医药卫生—放射医学]