Development of PSMA-1007-Related Series of 18F-Labeled Glu-Ureido-Type PSMA Inhibitors

被引：24

作者：

Cardinale, Jens ^{[1
]}

Roscher, Mareike ^{[1
]}

Schaefer, Martin ^{[1
]}

Geerlings, Max ^{[1
]}

Benesova, Martina ^{[1
]}

Bauder-Wuest, Ulrike ^{[1
]}

Remde, Yvonne ^{[1
]}

Eder, Matthias ^{[1
]}

Novakova, Zora ^{[2
]}

Motlova, Lucia ^{[2
]}

Barinka, Cyril ^{[2
]}

Giesel, Frederik L. ^{[3
]}

Kopka, Klaus ^{[4
]}

机构：

[1] German Canc Res Ctr, Div Radiopharmaceut Chem, D-69120 Heidelberg, Germany

[2] Czech Acad Sci, Lab Struct Biol, Inst Biotechnol, Vestec 25250, Czech Republic

[3] Univ Hosp Heidelberg, Dept Nucl Med, D-69120 Heidelberg, Germany

[4] Helmholtz Zentrum Dresden Rossendorf, Inst Radiopharmaceut Canc Res, D-01328 Dresden, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 63卷 / 19期

关键词：

GLUTAMATE-CARBOXYPEPTIDASE-II; UREA-BASED INHIBITORS; PROSTATE-CANCER; PRECLINICAL EVALUATION; RADIATION-DOSIMETRY; DIAGNOSIS; LIGAND; PET/CT; F-18-PSMA-1007; BIODISTRIBUTION;

D O I：

10.1021/acs.jmedchem.9b01479

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In recent years, a number of drugs targeting the prostate-specific membrane antigen (PSMA) have become important tools in the diagnosis and treatment of prostate cancer. In the present work, we report on the synthesis and preclinical evaluation of a series of F-18-labeled PSMA ligands for diagnostic application based on the theragnostic ligand PSMA-617. By applying modifications to the linker structure, insight into the structure-activity relationship could be gained, highlighting the importance of hydrophilicity and stereoselectivity on interaction with PSMA and hence the biodistribution. Selected compounds were co-crystallized with the PSMA protein and analyzed by X-rays with mixed results. Among these, PSMA-1007 (compound 5) showed the best interaction with the PSMA protein. The respective radiotracer [F-18]PSMA-1007 was translated into the clinic and is, in the meantime, subject of advanced clinical trials.

引用

页码：10897 / 10907

页数：11

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