A novel AlF-labelled NOTA-modified ubiquicidin 29-41 derivative as a bacterial infection PET imaging agent.

The antimicrobial peptide ubiquicidin 29-41 (TGRAKRRMQYNRR) is a potential target for detecting bacterial infection. A novel UBI 29-41 derivative modified with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) on the amino side of lysine was synthesized and radiolabelled with AlF, named [F]AlF-NOTA-UBI 29-41. The novel PET tracer maintained good in vitro stability in saline at room temperature and mouse serum at 37 °C.

Synthesis and Preclinical Evaluation of Novel Tc-Labeled FR-Targeting Agents with Satisfactory Imaging Contrast and Reduced Renal Uptake.

The folate receptor is overexpressed in a variety of epithelial-derived malignant cells. Several folate-based tracers have shown the ability to target FR, but excessive renal uptake is a general concern. To decrease renal uptake and achieve high target-to-nontarget ratios, two folate derivatives (DProFA and DAlaFA) were designed and synthesized.

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

To develop novel Tc-labeled ubiquicidin 29-41 derivatives for bacterial infection SPECT imaging aiming at achieving a high target-to-nontarget ratio and lower nontarget organ uptake, a novel 6-hydrazinoicotinamide (HYNIC) ubiquicidin 29-41 derivative (HYNIC-UBI 29-41) was designed and synthesized. It was then radiolabeled with ternary ligands, including TPPTS, PDA, 2,6-PDA, NIC, ISONIC, PSA, 4-PSA, and PES, to obtain eight Tc-labeled HYNIC-UBI 29-41 complexes. All the complexes demonstrated hydrophilicity, exhibited good stability, and specifically bound .

Influence of Linker Molecules on the Biodistribution Characteristics of Tc-labeled Mannose Derivatives with an Isocyanide-Coordinated Group.

A hallmark of cancer cells is their increased glucose demand, which is mediated by glucose transporters (GLUTs). Mannose is imported into cells via GLUTs, thereby prompting the selection of mannose as the targeting molecule for designing radioactive derivatives for tumor imaging. In this study, five Tc-labeled mannose derivatives were prepared and evaluated and .

Enantioselective Cobalt-Catalyzed Remote Hydroboration of Alkenylboronates.

Heteroatomic groups in alkenes typically direct thermodynamically favored chain walking of C═C bonds toward themselves, thereby facilitating C-H bond functionalization near the heteroatoms. We present herein an efficient cobalt-catalyzed contra-thermodynamic remote hydroboration of alkenylboronates with pinacolborane to synthesize chiral 1,-diboronates. This protocol features a broad substrate scope, high functional group tolerance, and excellent enantioselectivity.

Design and preclinical evaluation of Tc-Labeled dimer FAPI-46 derivatives as potential tumor radiotracers.

Fibroblast activation protein (FAP) is a crucial target for tumor diagnosis and treatment. FAP inhibitors (FAPIs) can selectively bind to FAP, and ligands with multiple targeting groups are anticipated to improve tumor-specific uptake. A dimeric FAPI ligand (L2) with high affinity for FAP was selected.

Novel technetium-99m-labelled ribociclib isocyanide derivatives for imaging cyclin-dependent kinase 4/6 (CDK4/6) expression in cancer.

Cyclin-dependent kinase 4/6 (CDK4/6) plays a crucial role in cell cycle regulation, is overexpressed in various cancers and is an important target in the development of radiotracers for tumour imaging. Despite the increasing recognition of CDK4/6 inhibitors in cancer therapy, their application is limited by the lack of suitable biomarkers. Herein, we developed a series of technetium-99m-labelled CDK4/6 radiotracers and utilized a linker optimization strategy to reduce their abdominal uptake and enhance their imaging properties.

The integration of optimizing train timetables with EMU route plans.

Generally, to address the resource management issues in high-speed railway operations, particularly in the context of large-scale networked high-speed train transportation organizations, a phased optimization approach is introduced. This approach divides the problem into two stages: the high-speed train timetabling and the planning of Electric Multiple Unit (EMU) route. The lack of direct integration between these stages has hindered the flexible and efficient utilization of line capacity and EMU resources based on large-scale network, limiting the potential for mutual compensation and coordination among different types of resources across different regions.

Development of Tc-Labeled Complexes with a Niraparib HYNIC Derivative for PARP-Positive Tumor Imaging.

As an enzyme that plays an 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 PARP-1 at lesion sites to help patients choose an appropriate treatment plan. In this work, niraparib was modified with a hydrazinonicotinamide (HYNIC) group to generate the ligand NPBHYNIC, which has an affinity (IC) of 450.

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.

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

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

Synthesis and Evaluation of Tc-Labeled Pro-Gly-Containing Tracers Targeting PSMA.

The specific expression of prostate-specific membrane antigen (PSMA) makes it an ideal target for the diagnosis and treatment of prostate cancer. Currently, many Tc-labeled PSMA-targeted tracers have been developed. However, the high renal uptake of these Tc-labeled tracers is a common problem that limits their clinical application.

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).

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.

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.