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

Current Advances in PARP1‐Targeted Theranostics

Journal of Labelled Compounds and Radiopharmaceuticals, Journal Year: 2025, Volume and Issue: 68(1-2)

Published: Jan. 1, 2025

Poly (ADP-ribose) polymerase 1 (PARP1) plays critical roles in DNA repair, chromatin regulation, and cellular equilibrium, positioning it as a pivotal target for therapeutic interventions cancer central nervous system (CNS) disorders. PARP1 responds to oxidative stress damage through PARylation, influencing energy depletion, survival, inflammation, genomic regulation many biological scenarios. PARP inhibitors (PARPis) have demonstrated efficacy against cancers harboring defective homologous recombination repair pathways, notably those linked BRCA mutations. PARP1-targeted PET imaging enables patient stratification, treatment assessment, PARPi pharmacodynamic evaluation other pathophysiological conditions. Importantly, theranostics emerged both diagnostic applications multiple types of cancers, representing advancement personalized oncology. However, its application brain tumors is limited by the heterogeneous integrity blood barrier (BBB) blood-tumor barrier. Thus, development BBB-penetrant tracers remains an unmet need cancers. This review summarizes current landscape radiopharmaceuticals radioligands targeting PARP1, detailing their pharmacological characteristics potential clinical uses. Furthermore, this discusses that can cross BBB, underscoring neurooncology neurological

Language: Английский

Synthesis and bioevaluation of a new 68Ga-labelled niraparib derivative that targets PARP-1 for tumour imaging

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 154, P. 108063 - 108063

Published: Dec. 12, 2024

Language: Английский