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.

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.

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.

Synthesis and Bioevaluation of Novel Technetium-99m-Labeled Complexes with Norfloxacin HYNIC Derivatives for Bacterial Infection Imaging.

To seek a novel Tc-labeled quinolone derivative for bacterial infection SPECT imaging that aims to lower nontarget organ uptake, a novel norfloxacin 6-hydrazinoicotinamide (HYNIC) derivative (HYNICNF) was designed and synthesized. It was radiolabeled with different coligands, such as tricine, trisodium triphenylphosphine-3,3',3″-trisulfonate (TPPTS), sodium triphenylphosphine-3-monosulfonate (TPPMS), and ethylenediamine-,'-diacetic acid (EDDA), to obtain three Tc-labeled norfloxacin HYNIC complexes, namely, [Tc]Tc-tricine-TPPTS-HYNICNF, [Tc]Tc-tricine-TPPMS-HYNICNF, and [Tc]Tc-EDDA-HYNICNF. These complexes were purified (RCP > 95%) and evaluated and for targeting bacteria.

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.

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%).

Preparation and Evaluation of Novel Folate Isonitrile Tc Complexes as Potential Tumor Imaging Agents to Target Folate Receptors.

In order to seek novel technetium-99m folate receptor-targeting agents, two folate derivatives (CN5FA and CNPFA) were synthesized and radiolabeled to obtain [Tc]Tc-CN5FA and [Tc]Tc-CNPFA complexes, which exhibited high radiochemical purity (>95%) without purification, hydrophilicity, and good stability in vitro. The KB cell competitive binding experiments indicated that [Tc]Tc-CN5FA and [Tc]Tc-CNPFA had specificity to folate receptor. Biodistribution studies in KB tumor-bearing mice illustrated that [Tc]Tc-CN5FA and [Tc]Tc-CNPFA had specific tumor uptake.

Radiolabeling and evaluation of a novel [TcN] complex with deferoxamine dithiocarbamate as a potential agent for bacterial infection imaging.

In order to find a Tc-labeled deferoxamine radiotracer for bacterial infection imaging, deferoxamine dithiocarbamate (DFODTC) was successfully synthesized and it was radiolabeled with [TcN] core to prepare the TcN(DFODTC) complex. TcN(DFODTC) was obtained with high radiochemical purity without further purification. The complex was lipophilic and exhibited good in vitro stability.

Finding Community Modules for Brain Networks Combined Uniform Design with Fruit Fly Optimization Algorithm.

There are a huge amount of neural units in brain networks. Some of the neural units have tight connection and form neural unit modules. These unit modules are helpful to the disease detection and target therapy.

Attribute index and uniform design based multiobjective association rule mining with evolutionary algorithm.

In association rule mining, evaluating an association rule needs to repeatedly scan database to compare the whole database with the antecedent, consequent of a rule and the whole rule. In order to decrease the number of comparisons and time consuming, we present an attribute index strategy. It only needs to scan database once to create the attribute index of each attribute.