Development of PET radiopharmaceuticals for pyrimidine'nucleotide metabolic imaging

尿嘧啶衍生物由于其广泛的药理学性质而引起了人们的极大兴趣，并且许多基于嘧啶的放射性药物已被开发用于单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，寻找新的或改进的胸腺嘧啶合成途径用于PET评价细胞增殖引起了人们的广泛关注。本文研究了一种简便高效的高比活性[^<11>C]COCl_2合成方法。^<11>C- labeled光气是引入^<11>C羰基形成多用途杂环化合物以及多种尿素的高效剂。我们已经证明了一种新的，有效的合成[2-^<11>C]嘧啶衍生物，包括[2-^<11>C]胸腺嘧啶和[2-^<11>C]5-FU，通过类似的方法，涉及光气的环缩合和关键中间体□-苯甲酰胺-□-取代丙烯酰胺，w . More可能作为肿瘤靶向PET示踪剂。该方法简便、温和、快速，产率高，为合成各种嘧啶衍生物提供了一种通用的方法。胸苷磷酸化酶（TP）的表达与肿瘤血管生成密切相关。为了开发一种基于ttp表达的PET放射示踪剂，用于癌症化疗的诊断和预后，我们合成了一种新型的^<11 bb0 C标记的氧咪唑烷基甲基尿嘧啶，它是在最有效的抑制剂之一5-溴-6-[（2-亚氨基咪唑烷基）甲基]氢溴化尿嘧啶（5BIMU）的基础上设计的，通过[^(11)C]光气与发达的二胺前体发生环闭合反应。经高效液相色谱纯化后，轰击后仅23 min就完成了全合成，合成结束时的产率为1653 MBq。该示踪剂具有TP抑制作用，可作为PET放射性药物用于血管生成酶TP表达成像。少

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