Synthesis and characterization of a novel 68 Ga-labeled p-bromobenzyl lysine-urea-ODAP PSMA inhibitor

Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synt...

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Bibliographic Details
Published inBioorganic & medicinal chemistry letters Vol. 91; p. 129382
Main Authors Sui, Yu, Duan, Xiaojiang, Zhang, Jingming, Chu, Yingming, Yang, Xing
Format Journal Article
LanguageEnglish
Published England 15.07.2023
Subjects
Animals
Antigens, Surface - metabolism
Cell Line, Tumor
Gallium Radioisotopes
Glutamate Carboxypeptidase II - metabolism
Humans
Ligands
Lysine - metabolism
Male
Mice
Positron-Emission Tomography - methods
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - metabolism
Tissue Distribution
Urea - chemistry
Prostate-specific membrane antigen (PSMA)
Imaging probe targeting PSMA
Oxalyldiaminopropionic acid-urea (ODAP-Urea)
Positron emission tomography
Prostate cancer
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Summary:Prostate-specific membrane antigen (PSMA) has been proved as a specific target for diagnosis and treatment of prostate cancer (PCa). Recently, oxalyldiaminopropionic acid (ODAP)-Urea-based ligands showed the potential as a new scaffold for developing radiotracers to image PCa. In this study, we synthesized seven ODAP-Urea-Lys derivatives characterized with p-bromobenzyl group conjugated to lysine. The ligands showed medium-to-high potency, with K values ranging from 27.9 nM to 0.94 nM. The ligands could be efficiently radiolabeled with Ga, in high purity. Radioligands were stable and showed PSMA specific cellular uptake, in PSMA LNCaP cells and PSMA 22Rv1 cells over PSMA PC3 cells. MicroPET imaging was performed in 22Rv1 tumor-bearing mice and Ga-ligand-1 showed the best characteristics among the seven ligands, with the highest tumor uptake (SUVmax: 0.56 ± 0.07). A biodistribution study was also performed. ODAP-Urea-Lys-p-bromobenzyl could be used to image prostate cancer in vivo, and the ligands could have high binding potency. The future investigation is still necessary to improve the tumor-specific uptake of this class of ligands and reducing the non-specific uptake in normal organs.
ISSN:1464-3405