肿瘤阳性显像剂^(111)In-pentetreotide的制备和动物实验

Preparation and experimental study of 111 Inpentetreotide

目的制备肿瘤阳性显像剂１１１Ｉｎｐｅｎｔｅｔｒｅｏｔｉｄｅ并进行实验研究。方法固相多肽合成法制备配体ｐｅｎｔｅｔｒｅｏｔｉｄｅ，正交实验确定１１１Ｉｎ标记药盒ＤＯＣＴ的组分及各组分间的配比，测定药盒及其标记产物１１１Ｉｎｐｅｎｔｅｔｒｅｏｔｉｄｅ的理化性质，建立相关的质控方法，并通过药理实验确定其生物性能和安全性。结果合成产物ｐｅｎｔｅｔｒｅｏｔｉｄｅ鉴定后制成用于１１１Ｉｎ标记的药盒；药盒在使用现场与１１１ＩｎＣｌ３溶液反应后，可得到标记率＞９９％的１１１Ｉｎｐｅｎｔｅｔｒｅｏｔｉｄｅ，并在室温下稳定至标记后８ｈ（放化纯度＞９５％）。正常小鼠分布实验显示１１１Ｉｎｐｅｎｔｅｔｒｅｏｔｉｄｅ有很快的血清除速率（注射后３０ｍｉｎ全血百分注射剂量＜１％）和较高的尿排泄（给药后４ｈ＞２０％）。荷胰腺癌裸鼠的生物分布和γ显像表明：显像剂的血液清除很快，放射性主要从泌尿系统排泄，给药后５ｍｉｎ膀胱显影，至３０ｍｉｎ双肾和膀胱的放射性达５０％ＩＤ；Ｔ／Ｂ比值在给药后逐渐增高，至８ｈ可达３６６，给药后１～２４ｈ均可进行荷胰腺癌裸鼠模型肿瘤阳性显像，４～８ｈ的图像质量最佳。结论研制的生长抑素受体肿瘤阳性显像剂１１?

Objective To prepare 111 Inpentetreotide for clinical applications Methods The pentetreotide was synthesized in our own laboratory An OctreoScanlike kit containing our synthetic pentetreotide and a set of other reagents were made for labeling with 111 In With the kit, 111 Inpentetreotide could be prepared on site Results The product showed high labeling yield (>99%) and good stability in vitro (>95% up to 8 h after reconstitution) Biological properties were evaluated by pharmacological experiments The rapid blood clearance (<1%ID/g by 30 min) and high urine excretion (>20%ID of renal up to 4 h post administration) were observed in biodistribution study of the normal mice Moreover, high T/B ratios (366 up to 8 h postinjection) and T/NT ratios (T/blood 409012, T/muscle 500021 by 4 h), as well as good quality images were demonstrated in a pancreas tumor bearing mouse model Conclusions The pentetreotide ligand, kit and its 111 In labeling product, prepared in our laboratory, have a good physicochemical and biological properties for the clinical application as an imaging agent of somatostatin receptor positive tumors