谷氨酸羧肽酶Ⅱ
前列腺癌
连接器
化学
药代动力学
多塔
体内
癌症研究
共轭体系
药理学
癌症
内科学
螯合作用
医学
生物技术
有机化学
计算机科学
生物
操作系统
聚合物
作者
Martina Benešová,Ulrike Bauder‐Wüst,Martin Schäfer,Karel D. Klika,Walter Mier,Uwe Haberkorn,Klaus Kopka,Matthias Eder
标识
DOI:10.1021/acs.jmedchem.5b01210
摘要
Since prostate-specific membrane antigen (PSMA) is up-regulated in nearly all stages of prostate cancer (PCa), PSMA can be considered as a viable diagnostic biomarker and treatment target in PCa. This project is focused on the development and evaluation of a series of compounds directed against PSMA. The modifications to the linker are designed to improve the binding potential and pharmacokinetics for theranostic application. In addition, the results help to further elucidate the structure-activity relationships (SAR) of the resulting PSMA inhibitors. Both in vitro and in vivo experiments of 18 synthesized PSMA inhibitor variants showed that systematic chemical modification of the linker has a significant impact on the tumor-targeting and pharmacokinetic properties. This approach can lead to an improved management of patients suffering from recurrent prostate cancer by the use of one radiolabeling precursor, which can be radiolabeled either with (68)Ga for diagnosis or with (177)Lu or (225)Ac for therapy.
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