Development of PET radiopharmaceuticals for pyrimidine'nucleotide metabolic imaging

嘧啶核苷酸代谢显像PET放射性药物的研制

基本信息

批准号：
17591288
负责人：
OHKURA Kazue
金额：
$ 2.44万
依托单位：
Health Sciences University of Hokkaido
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17591288/
关键词：
Nucleic acid Radiopharmaceuticals PET Nuclear medicine Tumor

项目摘要

Uracil derivatives are of considerable interest because of their wide array of pharmacological properties, and many pyrimidine-based radiopharmaceuticals have been developed for clinical diagnosis in the field of single photon or positron emission computed tomography. The search for new or improved synthetic routes leading to labeled thymidine for evaluation of cellular proliferation by PET has attracted much attention in recent years. Recently we have developed a simplified and highly efficient synthesis of [^<11>C]COCl_2 with high specific activity. ^<11>C-Labeled phosgene is a high-potency agent for the introduction of a ^<11>C carbonyl group to form versatile heterocyclic compounds as well as a variety of ureas.We have demonstrated a novel, efficient synthesis of [2-^<11>C]pyrimidine derivatives including [2-^<11>C]thymine and [2-^<11>C]5-FU, through an analogous method, involving cyclocondentaion of phosogene and the key intermediate □-benzoylamino-□-substituted acrylamides that w … More ould serve as a tumor targeting PET tracer. Because the method involves a simple, mild and rapid procedure, and the yields are essentially good, the present work would provide a general and useful synthesis of various pyrimidine derivatives.The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis in tumors. For developing a TP-expression-based PET radiotracer for diagnosis and prognosis of cancer chemotherapy, we synthesized a novel ^<11>C-labeled oxoimidazolidinylmethyluracil, which was designed on the basis of one of the most potent inhibitors, 5-bromo-6-[(2-iminoimidazolidinyl)methyl]uracil hydrobromide (5BIMU), through a ring closure reaction of [^(11) C]phosgene with a developed diamine precursor. After purification by HPLC, the total synthesis was accomplished in just 23 min after bombardment, and the yield was 1653 MBq at the end of synthesis. The new radiotracer can be used as a PET radiopharmaceutical for imaging angiogenic enzyme TP expression due to its TP inhibitory potency. Less

由于它们具有广泛的药理特性，因此尿嘧啶衍生物很有趣，并且许多基于嘧啶基的放射性药物已开发用于单个光子或正电子发射计算机断层扫描领域的临床诊断。近年来，寻找新的或改进的合成途径，用于评估胸腺胺以评估细胞增殖，引起了近年来的广泛关注。最近，我们开发了一种简单且高度发达的有效合成[^<11> c] COCL_2，具有高特异性活性。 ^<11>C-Labeled phosgene is a high-potency agent for the introduction of a ^<11>C carbonyl group to form versatile heterocyclic compounds as well as a variety of ureas.We have demonstrated a novel, efficient synthesis of [2-^<11>C]pyrimidine derivatives including [2-^<11>C]thymine and [2-^<11>C]5-FU, through an类似的方法，涉及哲原环体和关键的中间体□-Benzoylamino-□ - 取代的丙烯酰胺，这些丙烯酰胺会成为靶向宠物示踪剂的较高的丙烯酰胺。由于该方法涉及一个简单，温和和快速的程序，并且产量本质上是好的，因此目前的工作将提供各种嘧啶衍生物的一般且有用的合成。胸苷磷酸化酶（TP）的表达与肿瘤中的血管生成密切相关。开发一种基于TP表达的PET放射性示踪剂，用于癌症化学疗法的诊断和预后，我们合成了一种新型 ^<11> c标记的氧咪唑二唑磺胺甲基甲基尿素，该基于最有效的抑制剂之一，是5-溴-6--（2-氨基二氨基二胺）甲基化的（2-氨基酚），该基于5-溴-6-（2-溴）。通过[^（11）c] phosgene与发达的二胺前体的环闭合反应。 HPLC纯化后，总合成是在轰炸后仅23分钟内完成的，在合成结束时的产量为1653 MBQ。由于其TP抑制效力，新的放射性示踪剂可用作对血管生成酶TP的成像TP表达。较少的