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

Poly ADP-ribose polymerase (PARP) inhibitors prevent the repair of DNA single-strand breaks in cancer cells with abnormal homologous recombination, producing a synthetic lethal effect. Thus, PARP inhibitors have become clinically effective anticancer drugs. Labelling with radionuclides may extend the use of PARP inhibitors as tracers in nuclear medicine diagnostics, helping to stratify patients.

Current Status and Perspectives of Novel Radiopharmaceuticals with Heterologous Dual-targeted Functions: 2013-2023.

Radiotracers provide molecular- and cellular-level information in a noninvasive manner and have become important tools for precision medicine. In particular, the successful clinical application of radioligand therapeutic (RLT) has further strengthened the role of nuclear medicine in clinical treatment. The complicated microenvironment of the lesion has rendered traditional single-targeted radiopharmaceuticals incapable of fully meeting the requirements.

Development of a Novel Tc-Labeled Folate Derivative Containing Phenyl Isonitrile to Target Folate Receptor with Reduced Renal Uptake.

The folate receptor has attracted much attention in the field of radiolabeled imaging agents due to the significant difference in its expression levels between tumor cells and most normal cells. However, the development of folate-based imaging agents has been limited by their high uptake in the kidney. In this study, to reduce the high renal uptake of radiolabeled folate-based tracers, a phenyl-isonitrile folate derivative (CNMBFA) was designed and labeled with technetium-99m.

Corosolic acid inhibits EMT in lung cancer cells by promoting YAP-mediated ferroptosis.

Background: Corosolic acid (CA), a naturally occurring pentacyclic triterpenoid is renowned for its anticancer attributes. Previous studies have predominantly centered on the anticancer properties of CA in lung cancer, specifically its role in inducing apoptosis, however, investigations regarding its involvement in ferroptosis have been scarce.

Methods: The apoptotic and proliferative effects were evaluated by CCK8 and colony formation assay.

Novel Tc-Labeled Mannose Derivative as a Highly Promising Single Photon Emission Computed Tomography Probe for Tumor Imaging.

F-2-fluoro-2-deoxy-d-glucose ([F]FDG) has been the most used positron emission tomography imaging agent for clinical applications. Single photon emission computed tomography (SPECT) imaging is cheaper and used more widely for diagnostic use, but there is no SPECT tumor imaging agent for clinical applications comparable to [F]FDG. Mannose is a C2 epimer of glucose and can also be transported into tumor cells via glucose transporters (GLUTs).

Preparation and Evaluation of a Novel Tc-Labeled Niraparib Isonitrile Complex as a Potential PARP-1 Imaging Agent.

Poly ADP-ribose polymerase (PARP) plays an important role in the DNA repair process and has become an attractive target for cancer therapy in recent years. Given that niraparib has good clinical efficacy as a PARP inhibitor, this study aimed to develop radiolabeled niraparib derivatives for tumor imaging to detect PARP expression and improve the accuracy of stratified patient therapy. The niraparib isonitrile derivative (CNPN) was designed, synthesized, and radiolabeled to obtain the [Tc]Tc-CNPN complex with high radiochemical purity (>95%).

Synthesis and Preclinical Evaluation of Novel Tc-Labeled FAPI-46 Derivatives with Significant Tumor Uptake and Improved Tumor-to-Nontarget Ratios.

Fibroblast activation protein (FAP), which is expressed on the cell membranes of fibroblasts in most solid tumors, has become an important target for tumor diagnosis and treatment. However, previously reported Tc-labeled FAPI-04 complexes have high blood uptake, limiting their use in the clinic. In this work, six Tc-labeled FAPI-46 derivatives with different linkers (different amino acids, peptides, or polyethylene glycol) were prepared and evaluated.

Radiosynthesis and Bioevaluation of Tc-Labeled Isocyanide Ubiquicidin 29-41 Derivatives as Potential Agents for Bacterial Infection Imaging.

To develop a novel Tc-labeled ubiquicidin 29-41 derivative for bacterial infection single-photon emission computed tomography (SPECT) imaging with improved target-to-nontarget ratio and lower nontarget organ uptake, a series of isocyanide ubiquicidin 29-41 derivatives (CNnUBI 29-41, = 5-9) with different carbon linkers were designed, synthesized and radiolabeled with the [Tc]Tc(I) core, [Tc][Tc(I)(CO)(HO)] core and [Tc][Tc(V)N] core. All the complexes are hydrophilic, maintain good stability and specifically bind in vitro. The biodistribution in mice with bacterial infection and sterile inflammation demonstrated that [Tc]Tc-CN5UBI 29-41 was able to distinguish bacterial infection from sterile inflammation, which had an improved abscess uptake and a greater target-to-nontarget ratio.

The Preparation and Execution of Exploratory Human Studies on Novel Tc-Labeled Glucosamine Derivatives Containing Different Phenyl Isonitriles as Promising Tumor Imaging Agents.

As the "molecule of the century", 2-deoxy-2-[F]fluoro-d-glucose ([F]FDG) is a radioactive F-labeled glucose derivative with a wide range of applications for positron emission tomography (PET) imaging. Single photon emission computed tomography (SPECT) imaging is widely used, but there is no clinical probe comparable to [F]FDG. In our previous work, [Tc]Tc-CN5DG and [Tc]Tc-CN7DG were successfully developed and achieved high-quality SPECT images.

Preparation and Evaluation of [F]AlF-NOTA-PBB for PET Imaging of Cyclin-dependent Kinase 4/6 in Tumors.

Cyclin-dependent kinases (CDKs), especially cyclin-dependent kinase 4/6 (CDK4/6), have been targets for the development of specific tumor imaging agents. Palbociclib is a highly selective CDK4/6 inhibitor. In this study, to develop a novel F-labeled palbociclib derivative for specific tumor imaging, we designed and synthesized a ligand (NOTA-PBB) consisting of palbociclib as the targeted pharmacophore and NOTA as the macrocyclic bifunctional chelator.

Preparation and Bioevaluation of a Novel Tc-Labeled Glucose Derivative Containing Cyclohexane as a Promising Tumor Imaging Agent.

To develop novel tumor imaging agents with high tumor uptake and excellent tumor/non-target ratios, a glucose derivative containing cyclohexane (CNMCHDG) was synthesized and labeled with Tc-99m. [Tc]Tc-CNMCHDG was prepared by a kit formulation that was straightforward to operate and fast. Without purification, [Tc]Tc-CNMCHDG had a high radiochemical purity of over 95% and great in vitro stability and hydrophilicity (log P = -3.

A Simple Kit Formulation for Preparation and Exploratory Human Studies of a Novel Tc-Labeled Fibroblast Activation Protein Inhibitor Tracer for Imaging of the Fibroblast Activation Protein in Cancers.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment because it is selectively expressed on the cell membrane of cancer-associated fibroblasts in most solid tumor stroma. The aim of this study was to develop a Tc-labeled fibroblast activation protein inhibitor (FAPI) tracer, evaluate its imaging efficacy in nude mice, and further explore its biodistribution in healthy volunteers and uptake in tumor patients. An FAPI-derived ligand (DP-FAPI) containing d-proline was designed and synthesized as a linker, and a stable hydrophilic Tc-labeled complex ([Tc]Tc-DP-FAPI) was obtained by kit formulation.

Synthesis and Evaluation of Tc-Labeled FAP Inhibitors with Different Linkers for Imaging of Fibroblast Activation Proteins in Tumors.

Fibroblast activation protein (FAP) is a potential target for tumor diagnosis and treatment due to its selective expression on cancer-associated fibroblasts (CAFs) in most solid tumor stroma. Two FAP inhibitor (FAPI) derived ligands (L1 and L2) containing different lengths of Pro-Gly (PG) repeat units as linkers were designed and synthesized with high affinity for FAP. Two stable hydrophilic Tc-labeled complexes ([Tc]Tc-L1 and [Tc]Tc-L2) were obtained.

Current status and progress in using radiolabelled PARP-1 inhibitors for imaging PARP-1 expression in tumours.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a key enzyme in the DNA repair process, and the overexpression of PARP-1 in several tumours makes this enzyme a promising molecular target. Recently, several PARP-1 inhibitors, such as olaparib, rucaparib, niraparib and talazoparib, have been clinically approved as anticancer drugs. Several of these inhibitors have been radiolabelled for noninvasive imaging of PARP-1 expression in several types of tumours.

Novel Tc labeled complexes with bisphosphonate isocyanide: Radiosynthesis and evaluation as potential bone-seeking agents.

In order to develop Tc-labeled complexes with bisphosphonate isocyanide as novel bone imaging agents, two bisphosphonate isocyanide derivatives (CNALN and CNPAM) were synthesized and radiolabeling was performed for preparing the corresponding [Tc]Tc(I) complexes. [Tc]Tc-CNALN and [Tc]Tc-CNPAM were obtained with high radiochemical purity and showed good in vitro stability. Both of them were hydrophilic and had high affinity to hydroxyapatite.

A Study on Curcumol Influencing Proliferation and Apoptosis of Hepatocellular Carcinoma Cells through DJ-1/PTEN/PI3K/AKT Pathway.

Objective: To study the mechanism of curcumol affecting the proliferation and apoptosis of liver cancer cells through the DJ-1/PTEN/PI3K/AKT pathway.

Method: HepG2 cells were cultured in vitro, treated with curcumol at concentrations of 10, 30, and 100 g/mL, and DMSO was used as a control. The levels of cell proliferation and apoptosis were measured by CCK-8 and flow cytometry, respectively.

Preparation and Bioevaluation of Tc-Labeled FAP Inhibitors as Tumor Radiotracers to Target the Fibroblast Activation Protein.

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts (CAFs) in a majority of human epithelial cancers. With low expression in normal organs, FAP has become a promising molecular target for tumor theranostics. To develop a lower cost and more widely available alternative to positron emission tomography (PET), two isocyanide-containing FAP inhibitors (CN-C-FAPI and CN-PEG-FAPI) were synthesized and radiolabeled with Tc to obtain [Tc][Tc-(CN-C-FAPI)] and [Tc][Tc-(CN-PEG-FAPI)] in high yields (>95%).

Colorimetric detection of glutathione based on its inhibitory effect on the peroxidase-mimicking properties of WS nanosheets.

A highly sensitive colorimetric assay is described for the determination of glutathione (GSH). It is based on the use of tungsten disulfide (WS) which is a peroxidase mimic. It catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by hydrogen peroxide to form a blue-colored product (oxTMB) at near neutral pH values.

MicroRNA-223-3p Regulates Ovarian Cancer Cell Proliferation and Invasion by Targeting SOX11 Expression.

MicroRNAs (miRNAs) often display different expression in many cancers and other diseases in current research studies. miR-223 expression is upregulated in rheumatoid arthritis. Also, miR-223 expression has been demonstrated to be highly expressed in pancreatic cancer and gastric cancer in comparison with normal tissue.