糖基化生长抑素99Tcm标记及生物学评价

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⁹⁹Tc^m标记，重点探讨⁹⁹Tc^m标记条件及标记物体外稳定性；并用⁹⁹Tc^m-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，⁹⁹Tc^m-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；⁹⁹Tc^m-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，⁹⁹Tc^m-Cysteamine-Dx¹⁰-SMS有望成为一种生长抑素受体阳性肿瘤显像剂。

Labeling of Glycosylated Somatostatin With 99Tcm and Its Biological Evaluation

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.