(S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic Acid as a Novel PSMA Targeting Scaffold for Prostate Cancer Imaging

Abstract

In an effort to seek novel agents targeting prostatespecific membrane antigen (PSMA), 16 ligands (L1−L16) with structural modifications in S1′ binding pocket were synthesized and evaluated for PSMA inhibition. (S)-3-(Carboxyformamido)-2-(3-(carboxymethyl)ureido)propanoic acids proved to be potent PSMA ligands with K i values ranging from 0.08 nM to 8.98 nM, which are in the range of or are higher in potency compared to previously published urea-based ligands. Computational docking was performed to study the binding mode of the two most potent ligands discovered. FITC-conjugated L14 could selectively stain PSMA + LNCaP cells over PSMA − PC3 cells. IRDye800CW conjugated L16 can effectively image tumors in a murine xenograft model of prostate cancer.

Current status and future perspective of radiopharmaceuticals in China

“…In an effort to seek novel agents targeting PSMA, based on oxalyldiaminopropionic acid (ODAP), 16 ligands with structural modifications in PSMA S1′ binding pocket were synthesized and evaluated for PSMA inhibition by Duan et al (S)-3-(carboxyformamido)-2-(3-(carboxymethyl)ureido) propanoic acids prove to be potent PSMA ligands with Ki values ranging from 0.08 to 8.98 nM [44]. Twelve ODAPurea-based ligands were synthesized and radiolabeled with 68 Ga [22].…”

Application Analysis of 124I-PPMN for Enhanced Retention in Tumors of Prostate Cancer Xenograft Mice

“…The PSMA small molecule inhibitors used in our study were designed independently based on the latest research. 14 It is challenging for metal-based nanoparticles to achieve clinical applications due to unpredictable toxicity and side effects while needing to maintain high stability. 15 Melanin is a ubiquitous, amorphous, irregular functional biopolymer in nature.…”

Preparation and Biological Evaluation of [99mTc]Tc-CNGU as a PSMA-Targeted Radiotracer for the Imaging of Prostate Cancer

“…The PSMA inhibitory activity was analyzed according to the previously described method of fluorescence-based Amplex Red glutamic acid assay [10]. The lysates of the LNCaP cell extracts (30 µL), CNGU (15 µL, changeable concentrations from 0.01 nM to 1 µM) and N-acetylaspartylglutamate (3.5 µM, 15 µL) were mixed in a 96-well plate and incubated at 37 • C for 2 h. The glutamate concentration was obtained according to the result of incubating with a standard solution (50 µL) of the Amplex Red glutamic acid test kit for 30 min.…”

“…Radiolabeled antibodies usually exhibit some shortcomings, such as long circulation times and a slow clearance from non-targeted organs and tissues [9]. Small molecular prostate cancer imaging agents present superior pharmacokinetics, as they accumulate quickly on tumor lesions and have a higher permeability via internalization [10]. New radioactive imaging agents bearing a glutamate-urea-based PSMA-targeted Molecules 2020, 25, 5548 2 of 11 ligand are considered reliable radiolabeled tracers in clinical trials [11].…”