Optimization Of Parameters For Tumor-targeting Of Radio-

无线电肿瘤靶向参数的优化

• 批准号: 6825899
• 负责人: Chang Hum Paik
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6825899
• 关键词: biological transport; chemical conjugate; chemical kinetics; chemical models; chemical reaction; clearance rate; laboratory mouse; neoplasm /cancer radiation therapy; polymers; radiation sensitivity; radiobiology; radiotracer; whole body irradiation effect

The overall purpose of our research was to improve the tumor targeting properties of radiolabeled biologicals by optimizing chemical parameters. This year we developed a semi-automated 3-column system to purify a positron emitter,Y-86 because it is a better surrogate radionuclide than In-111 currently in use to estimate dosimetry of Y-90-labeled therapeutic radiopharmaceuticals. This purification system involved the passage of Cyclotron produced Y-86 samples through a Sr-selective Sr-Spec column, a Y-selective RE-Spec column and finally a cation-exchange Aminex A5 column connected in series. This method enabled us to decontaiminate Sr by 250,000 times with >80% recovery of Y-86. We also investigated a new Tc-99m chemistry involving [Tc-99m (OH)3(CO)3]+ with Tc-99m (I) oxidation state to label biological molecules under mild conditions. The three water molecules of this complex are labile and can be substituted by a molecule with two or three coordination sites to form a stable ellipsoidal Tc-99m complex. We optimized the chemical condition to label norbiotinamido-DTPA and -EDTA with Tc-99m at 45 degree C. The animal study indicates that this approach is promising to synthesize a polar Tc-99m labeled biotin that rapidly accumulates in tumors with pretargeted antibody-streptavidin while being excreted via the renal system.

我们研究的总体目的是通过优化化学参数来提高放射性标记生物制剂的肿瘤靶向性。今年，我们开发了一个半自动的3柱系统来纯化正电子发射体，Y-86，因为它是一个更好的替代放射性核素比In-111目前使用的Y-90标记的治疗放射性药物的剂量估计。该纯化系统包括使回旋加速器产生的Y-86样品通过串联连接的Sr-选择性Sr-Spec柱、Y-选择性RE-Spec柱和最后的阳离子交换Aminex A5柱。该方法使我们能够将Sr反萃250，000倍，Y-86的回收率>80%。我们还研究了一种新的Tc-99 m化学反应，涉及具有Tc-99 m（I）氧化态的[Tc-99 m（OH）3（CO）3]+，以在温和条件下标记生物分子。该配合物的三个水分子是不稳定的，可以被具有两个或三个配位位点的分子取代，形成稳定的椭球形Tc-99 m配合物。优化了45 ℃下99 m Tc标记去甲生物素酰胺-DTPA和-EDTA的化学条件。动物研究表明，这种方法有希望合成一种极性Tc-99 m标记的生物素，该生物素在具有预靶向抗体-链霉亲和素的肿瘤中快速积累，同时通过肾脏系统排出。