Synthesis and preclinical evaluation of 68 Ga-labeled PSMA tracers with improved pharmacological properties

Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2024-08, Vol.274, p.116545
Main Authors: Hou, Haodong, Lin, Yixiang, Pan, Yuan, Ma, Yuze, Hou, Guihua, Sun, Xiangyang, Gao, Feng
Format: Article
Language:English
Subjects:
Animals
Antigens, Surface - metabolism
Cell Line, Tumor
Gallium Radioisotopes - chemistry
Glutamate Carboxypeptidase II - antagonists & inhibitors
Glutamate Carboxypeptidase II - metabolism
Humans
Male
Mice
Molecular Structure
Positron Emission Tomography Computed Tomography
Prostatic Neoplasms - diagnostic imaging
Prostatic Neoplasms - drug therapy
Prostatic Neoplasms - pathology
Radiopharmaceuticals - chemical synthesis
Radiopharmaceuticals - chemistry
Radiopharmaceuticals - pharmacology
Tissue Distribution
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Summary:Prostate cancer (PCa) is one of the most common tumors in men, with the overexpression of prostate-specific membrane. In this study, we developed four new Ga-labeled PSMA-targeting tracers by introducing quinoline, phenylalanine and decanoic acid groups to enhance their lipophilicity, strategically limiting their metabolic pathway through the urinary system. Four radiotracers were synthesized with radiochemical purity >95 %, and exhibited high stability in vivo and in vitro. The inhibition constants (K ) of SDTWS01-04 to PSMA were in the nanomolar range (
ISSN:1768-3254
DOI:10.1016/j.ejmech.2024.116545