Development of radioiolabeled uracil derivatives as radionuclide therapeutic agents for thymidine phosphorylase expressing tumors

放射性核素治疗是治疗和延长癌症患者生命的一种有利方法。胸苷磷酸化酶（TP）的表达与血管生成和肿瘤侵袭密切相关。为了开发体内TP靶向放疗的放射性药物，合成了几种放射性碘化TP抑制剂。虽然放射性碘化的5-碘-6-（氧咪唑烷基）甲基尿嘧啶衍生物在体外评估后显示出成功的结果，但体内评估的结果不足以用于放射性核素治疗。为了解决TP指示性生理表达在肝脏中的高放射性问题，设计了一种前药，通过肿瘤中过表达的酶转化为强TP抑制剂。尽管需要进行大量的调查，但从本研究中获得的方法将为体内tp靶向放疗的发展铺平道路。

Radionuclide therapy is a propitious method for treating and prolonging the lives of patients with cancer. The expression of thymidine phosphorylase (TP) is closely associated with angiogenesis and tumor invasiveness. To develop radiopharmaceuticals for in vivo TP-targeting radiotherapy, several radioiodinated TP inhibitors were synthesized. Although the radioiodinated 5-iodo-6-(oxoimidazolidinyl)methyluracil derivative showed successful results following in vitro evaluations, the results of in vivo evaluations were inadequate for radionuclide therapy. To solve the problem of high radioactivity in the liver due to indicative physiological TP expression, a prodrug was designed to undergo conversion into a strong TP inhibitor by an enzyme overexpressed in the tumor. Although substantial investigations are required, the approach obtained from this study will pave the way for the development of in vivo TP-targeted radiotherapy.