Development of ^99mTc-Labeled Complexes with a Niraparib HYNIC Derivative for PARP-Positive Tumor Imaging

Molecular Pharmaceutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

As an enzyme that plays important role in DNA repair, poly(ADP-ribose) polymerase-1 (PARP-1) has become a popular target for cancer therapy. Nuclear medicine molecular imaging technology, supplemented by radiolabeled PARP-1 inhibitors, can accurately determine the expression level of at lesion sites to help patients choose appropriate treatment plan. In this work, niraparib was modified with hydrazinonicotinamide (HYNIC) group generate ligand NPBHYNIC, which vitro affinity (IC50) 450.90 nM PARP-1. The NPBHYNIC labeled technetium-99m and six different coligands yield [99mTc]Tc-(X/tricine)-NPBHYNIC (X = TPPTS, TPPMS, PSA, PDA, NIC ISONIC). These complexes were hydrophilic exhibited good stability vitro, low levels these taken up nontarget organs tissues Kunming mice. Among complexes, [99mTc]Tc-(TPPTS/tricine)-NPBHYNIC [99mTc]Tc-(NIC/tricine)-NPBHYNIC selected biodistribution HeLa tumor-bearing BALB/c nude mice 2 h post injection. results revealed tumor uptake (1.02 ± 0.07% ID/g) greater than (0.36 0.05% ID/g). Additionally, biodistribution, single-photon emission computed tomography/computed tomography (SPECT/CT) radioautography experiments, significantly reduced blocked group, indicating specificity. Therefore, it potential use as niraparib-based agent targets

Language: Английский

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Development of Novel ^99mTc-Labeled Hydrazinoicotinamide-Modified Ubiquicidin 29-41 Complexes with Improved Target-to-Nontarget Ratios for Bacterial Infection Imaging

ACS Pharmacology & Translational Science, Journal Year: 2025, Volume and Issue: 8(2), P. 470 - 483

Published: Feb. 4, 2025

To develop novel 99mTc-labeled ubiquicidin 29-41 derivatives for bacterial infection SPECT imaging aiming at achieving a high target-to-nontarget ratio and lower nontarget organ uptake, 6-hydrazinoicotinamide (HYNIC) derivative (HYNIC-UBI 29-41) was designed synthesized. It then radiolabeled with ternary ligands, including TPPTS, PDA, 2,6-PDA, NIC, ISONIC, PSA, 4-PSA, PES, to obtain eight HYNIC-UBI complexes. All the complexes demonstrated hydrophilicity, exhibited good in vitro stability, specifically bound Staphylococcus aureus vitro. Biodistribution studies mice that [99mTc]Tc-tricine/TPPTS-HYNIC-UBI resulted increased abscess-to-muscle abscess-to-blood ratios as well decreased uptake. Furthermore, it able distinguish between sterile inflammation. Single-photon emission computed tomography (SPECT) revealed visible accumulation site of infection, indicating is potential radiotracer infection.

Language: Английский

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Synthesis and Evaluation of ^99mTc-Labeled _DPro-Gly-Containing Tracers Targeting PSMA

Molecular Pharmaceutics, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 19, 2024

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment prostate cancer. Currently, many

Language: Английский

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Synthesis and Evaluation of ^99mTc-Labeled l-Aspartic Acid as a EuK Polymer Linker for Targeting PSMA to a Novel SPECT Tumor Tracer

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(23), P. 21617 - 21628

Published: Dec. 3, 2024

The development of novel tracers targeting prostate-specific membrane antigen (PSMA) has great potential for improving the diagnosis and treatment prostate cancer (PCa). This study aimed to improve absolute tumor uptake tumor-to-background ratios (TBRs) this PSMA tracer by increasing number pharmacophores, Glu-urea-Lys (EuK), that specifically bind PSMA. We successfully synthesized four radioligands prepared a total 12 stable radiotracers coordinating

Language: Английский

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