~(99m)Tc标记生长抑素类似物KE108的制备及生物学评价

为了探讨生长抑素类似物~(99m)Tc-HYNIC-KE108用于生长抑素受体阳性肿瘤显像的可行性,本研究设计合成了新型的生长抑素类似物HYNIC-KE108,并进行~(99m)Tc标记,优化标记条件,测定标记物的脂水分配系数和体外稳定性,研究其在正常小鼠及荷瘤鼠体内的生物分布。在优化条件下,~(99m)TcHYNIC-KE108的标记率90%,经Waters Oasis HLB小柱纯化后,放化纯度98%,标记物的脂水分配系数logP为0.43±0.02(n=3),体外稳定性良好。标记物在正常小鼠体内血液清除快,主要通过肾脏代谢,在胃、肺和肝脏中放射性摄取相对较高。荷瘤鼠体内分布结果表明,标记物注入体内4h时在肿瘤中的放射性摄取为(1.14±0.91)%ID·g-1,肿瘤与血、肌肉、心脏的放射性摄取比(T/NT)为1.78、8.14、3.35。本工作为进一步研究~(99m)Tc标记的KE108作为生长抑素受体阳性肿瘤显像剂提供了实验依据。

Preparation and Biological Evaluation of 99mTc Labeled Somatostatin Analogue 99mTC-HYNIC-KE108

Most tumor cells overexpress somatostatin receptors.It is well known that somatostatin and its analogues can bind to somatostatin receptors specifically.Therefore,radionuclide-labeled somatostitin and its analogues may be used for the early diagnosis of somatostatin receptor positive tumours.In order to explore the feasibility of somatostatin analogues HYNIC-KE108 for somatostatin receptor positive tumor imaging,the new somatostatin analogue 99mTc-HYNIC-KE108 was designed and synthesized.The lipid water partition coefficient and in vitro stability of the markers were determined.The biological studies were carried out in normal mice and also in tumorbearing nude mice.The labelling yield of 99mTc-HYNIC-KE108 was approximately 90％ under the optimized conditions,and the radiochemical purity was more than 98％ after Waters Oasis HLB colunm purification.The lipid-water partition coefficient of the marker LogP was 0.43±0.02 (n=3).The labelled complex showed satisfactory stability in vitro.99mTc-HYNIC-KE108 displayed a rapid blood and metabolized by kidneys.Meanwhile,the substantial uptakes of radioactivity in stomach,lung and liver were observed.The biodistribution of the labeled compound in tumor-bearing mice was 1.14±0.91(％ID · g-1) at 4 h after injection.There was high radioactivity uptake in tumor and rapid blood clearance,and thus high ratios of tumor to blood and muscle were obtained at 4 h post injection.The tumor-to-normal tissue ratio (T/NT) for blood,muscle and heart were 1.78,8.14 and 3.35,respectively.All these results indicate that 99mTc-HYNIC-KE108 is a novel promising candidate for somatostatin receptor positive tumor imaging.