糖基化生长抑素99Tcm标记及生物学评价

    Labeling of Glycosylated Somatostatin With 99Tcm and Its Biological Evaluation

    • 摘要: 以天然生长抑素(Somatostatin,SMS)、葡聚糖-10(Dextran10,Dx10)及巯基乙胺(Cysteamine)为原料,合成糖基化生长抑素配体化合物SMS-Dx10-Cysteamine;以125I-奥曲肽(125I-Tyr3-Octreotide)为放射性配基,进行受体竞争结合实验,测定SMS-Dx10-Cysteamine的IC50值;利用葡庚糖转换络合进行SMS-Dx10-Cysteamine 的99Tcm标记,重点探讨99Tcm标记条件及标记物体外稳定性;并用99Tcm-Cysteamine-Dx10-SMS进行正常SD大鼠体内分布、血浆清除及肿瘤模型动物显像实验。结果表明:配体化合物SMS-Dx10-Cysteamine保持了对生长抑素2型受体高亲和力,其IC50值与SMS相近;在最佳标记条件:0.3 g/L SnCl2,5 g/L SMS-Dx10-Cysteamine,标记介质pH=6.0,室温下反应30 min,99Tcm-Cysteamine-Dx10-SMS标记率约为85%,经分离纯化后,其放射化学纯度大于99%,标记物体外稳定;99Tcm-Cysteamine-Dx10-SMS在正常大鼠体内血浆半衰期为2.38 h,主要浓聚于肝、脾脏并经肾排泄;荷胰腺癌裸鼠显像表明,注射后6 h,肿瘤组织具有明显的放射性摄取,99Tcm-Cysteamine-Dx10-SMS有望成为一种生长抑素受体阳性肿瘤显像剂。

       

      Abstract: Natural somatostatin (SMS), dextran-10(Dx10) and cysteamine were used to synthesis somatostatin-dextran-cysteamine (SMS-Dx10-Cysteamine) conjugate. The in vitrosomatostatin receptor competition binding study was carried out by using 125I-Tyr3-Octreotide as a radioligand to measure the IC50value of SMS-Dx10-Cysteamine. The SMS-Dx10-Cysteamine was radiolabeled with 99Tcm by using gluconate as a transchelator. The radiolabeling conditions of 99TcmCysteamine-Dx10-SMS and its in vitrostability were studied in detail. The biodistribution and blood halflife of 99Tcm-Cysteamine-Dx10-SMS were investigated in normal rats and its tumor uptake and imaging properties were evaluated in nude mice bearing human pancreatic tumor. The results show that SMS-Dx10-Cysteamine remained high receptor binding affinity to somatostatin receptor subtype 2, and the IC50value is in the same range as somatostatin. The radiolabeling efficiency of 99Tcm-CysteamineDx10-SMS is about 85% under optimum conditions and its radiochemical purity is more than 99% after purification. The blood halflife of 99Tcm-Cysteamine-Dx10-SMS in normal rats is 2.38 h post injection. The digestion and excretion is mainly through the hepatobiliary and kidney system. The 99Tcm-Cysteamine-Dx10-SMS is localized in pancreatic tumor and show visible tumor uptake at 6 h imaging. The results indicate that 99Tcm-Cysteamine-Dx10-SMS is a promising imaging agent candidate for somatostatin receptor positive tumor.

       

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