22 results about "Bifunctional chelator" patented technology

The application discloses a polypeptide PET molecular probe for targeting breast cancer and a preparation method and application thereof. The polypeptide PET molecular probe for targeting breast cancer is obtained by labeling an AR polypeptide modified by a bifunctional chelating agent with a positron emitting radionuclide, and has the advantages of simple synthesis, small molecular weight, high specificity, no immunogenicity and good biological safety. In addition, the polypeptide PET molecular probe has high radiochemical performance and in-vivo and in-vitro stability, can better realize breast cancer targeted PET imaging compared with current commonly used imaging agents, can be used for preparing an imaging agent for breast cancer diagnosis, and is helpful for clinical diagnosis of breast cancer.

The invention discloses a radioactive diagnosis medicine for targeting OPN as well as a preparation method and application of the radioactive diagnosis medicine. The radioactive diagnosis medicine comprises linear polypeptide and radionuclide, wherein the linear polypeptide is composed of 20 L-type amino acids and one D-type amino acid, and the radionuclide marks the linear polypeptide through a bifunctional chelating agent; the sequence of the linear polypeptide is as shown in SEQ ID NO. 1. In vivo, radionuclides in the medicine are concentrated to an atherosclerotic vulnerable plaque part through the targeting effect of the amino acid linear polypeptide, and imaging diagnosis is carried out on the atherosclerotic vulnerable plaque by utilizing a positron emission computed tomography technology of nuclear medicine.

Disclosed are a myocarditis-targeted radionuclide molecular probe, a preparation method therefor, and an application thereof. The myocarditis-targeted radionuclide molecular probe includes a DPP4 inhibitor, a bifunctional chelator covalently bonded to an amino group of the DPP4 inhibitor, and a metallic radionuclide coordinately bonded to the bifunctional chelator. The myocarditis-targeted radionuclide molecular probe provided by the present disclosure exhibits high specificity and good targeting capability, and demonstrates significant uptake in myocardial inflammatory cells, and low uptake in non-target tissues. Characterized by high resolution and sensitivity of imaging, the myocarditis-targeted radionuclide molecular probe is applied for early diagnosis of cardiac inflammatory infiltration severity, therapeutic efficacy evaluation, prognosis assessment and the like, and has promising clinical and application prospects in the field of non-invasive nuclear medicine diagnosis and treatment as a myocarditis imaging agent.

The invention relates to the technical field of radiopharmaceutical research and development, and discloses a radiotargeted nuclide drug molecule design method based on a first principle, comprising: screening a high-specificity target based on a preset demand, and screening candidate nuclides according to drug functions and ligand types corresponding to the high-specificity target; the method comprises the following steps: setting a difunctional chelating agent adaptive to candidate nuclides, setting a ligand for a high-specificity target, setting a linker for connecting the difunctional chelating agent and the ligand, calculating and optimizing the difunctional chelating agent, the ligand and the linker according to a first principle, and assembling according to a nuclide-chelating agent-linker-ligand sequence to obtain an initial molecular complex; and for alpha nuclide in the initial molecular complex, calculating and optimizing through a first principle to obtain a target molecular complex. According to the method, by constructing collaborative design logic, the drug targeting property, stability and the balance capacity of the curative effect and safety are improved, special optimization is carried out for alpha nuclide risks so as to reduce toxicity, and extensive expandability is achieved.

The invention provides an LAG-3 targeted diagnosis and treatment integrated molecular imaging probe as well as a preparation method and application thereof. The preparation method comprises the following steps: (1) carrying out ultrafiltration on an anti-human LAG-3 monoclonal antibody by using a buffer solution; adding a bifunctional chelating agent for reaction, and performing ultrafiltration purification to obtain a labeled precursor DOTA-alphaLAG-3; (2) mixing the labeled precursor DOTA-alphaLAG-3 with a buffer solution, and then adding radionuclide for reaction; and after the reaction is finished, carrying out ultrafiltration purification on the obtained reaction liquid to obtain the LAG-3 targeted diagnosis and treatment integrated molecular imaging probe. The obtained LAG-3 targeted diagnosis and treatment integrated molecular imaging probe can play a synergistic anti-tumor effect with immunotherapy.

Provided herein are use of an exosome, a complex comprising an exosome, a tracer, and a preparation method and use thereof. The complex comprises an exosome, a bifunctional chelating agent coupled to the exosome, and a radionuclide gallium-67 or gallium-68 embedded on the bifunctional chelating agent. In a preferred implementation, the bifunctional chelating agent comprises 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).

The invention provides a Nectin-4-targeted bicyclopeptide nuclide ligand, a probe as well as a preparation method and application of the Nectin-4-targeted bicyclopeptide nuclide ligand and the probe, and the Nectin-4-targeted bicyclopeptide nuclide ligand and the probe are used for imaging diagnosis of Nectin-4 positive tumor patients, and can realize medication guidance and real-time curative effect monitoring of the patients receiving anti-cancer drug treatment; a pharmacokinetic modified molecule polyethylene glycol is added between a chelating agent for radionuclide labeling and a Nectin-4 targeted polypeptide, so that the biocompatibility of the probe is improved, and the pharmacokinetic property, particularly the removal kinetics of non-tumor tissues, is optimized, so that a better diagnosis and treatment effect is achieved; according to the bicyclic peptide nuclide ligand DOTA-PEG-bicyclic peptide disclosed by the invention, DOTA is used as a bifunctional chelating agent, so that the bicyclic peptide nuclide ligand DOTA-PEG-bicyclic peptide has better in-vivo and in-vitro stability.

The invention provides a Nectin-4-targeted bicyclopeptide nuclide ligand, a probe as well as a preparation method and application of the Nectin-4-targeted bicyclopeptide nuclide ligand and the probe, the Nectin-4-targeted bicyclopeptide nuclide ligand and the probe are used for imaging diagnosis of Nectin-4 positive tumor patients, and medication guidance and real-time curative effect monitoring of the patients receiving anti-cancer targeted drug treatment can be realized; according to the present invention, the pharmacokinetic modification molecule polysarcosine is added between the chelating agent for radionuclide labeling and the Nectin-4 targeting polypeptide, such that the biocompatibility of the probe is improved, and the pharmacokinetic property, especially the non-tumor tissue removal kinetics, is optimized so as to achieve the good diagnosis and treatment effect; the bicyclic peptide nuclide ligand DOTA-Sar-bicyclic peptide provided by the invention uses DOTA as a bifunctional chelating agent, so that the bicyclic peptide nuclide ligand DOTA-Sar-bicyclic peptide has better in-vivo and in-vitro stability.

This invention relates to a method for preparing and applying a radiopharmaceutical containing an interleukin-2 mutant, specifically belonging to the field of molecular biology pharmaceuticals. The radiopharmaceutical comprises the interleukin-2 mutant (sIL-2), a radionuclide, and a chelating agent. The radionuclide is labeled with GGGGK-HYNIC and linked to the LPETG tag of sIL-2 under the action of Sortase A enzyme. This invention is based on a radiopharmaceutical prepared from an interleukin-2 mutant. Through protein sequence mutation, the resulting mutant sIL-2 exhibits lower toxicity than interleukin-2 (IL-2) and higher receptor affinity, which is more conducive to T cell imaging in vivo. Site-specific labeling of the radionuclide using Sortase A enzyme and residual cysteine ​​residues at the C-terminus of the protein structure ensures the homogeneity of the prepared radiopharmaceutical. Furthermore, HYNIC is used as a bifunctional chelating agent, and TPPTS and tricine are used as co-ligands to achieve… 99m The Tc-HYNIC core exhibits better in vivo and in vitro stability.

This invention discloses a method for deashing polyolefins based on the synergistic effect of a bifunctional chelating agent and periodic supercritical CO2, belonging to the field of polyolefin material preparation technology. First, a bifunctional chelating agent with both CO2 affinity and metal chelating ability is synthesized. Then, polypropylene material and the chelating agent are placed in a high-pressure reactor, CO2 is injected, and the temperature and pressure are increased to a supercritical state. Under the condition of maintaining the supercritical temperature, the pressure is periodically controlled, causing the pressure to pulsate between high and low pressure, sequentially experiencing a swelling / permeation stage and an expansion / elution stage. After the cycle is completed, the pressure is released, and high-purity polypropylene is obtained after post-treatment. This invention transforms static diffusion mass transfer into forced convection mass transfer through periodic pressure control, achieving deep removal of metal residues with a removal rate as high as 97.14%. The total ash content of the product can be reduced to 5.29 ppm, with no significant impact on the properties of the polypropylene itself. It also features short processing time and significant environmental advantages.

The invention discloses a DSG2-targeted nuclide diagnosis and treatment integrated probe as well as a preparation method and application thereof, and the DSG2-targeted nuclide diagnosis and treatment integrated probe takes two serially connected cyclic peptides as a core targeting structure, and a DSG2-targeted radiolabeled complex can be obtained by labeling nuclide through a bifunctional chelating agent. Experimental results show that the complex is expected to be applied to DSG2 targeted nuclide diagnosis and treatment as a probe.

The present invention provides a carrier platform functionalized with a chelating agent. The carrier platform has a Formula I as follows: ITP- Pu According to Formula I, ITP represents an integrin-targeting peptide that comprises cRGD, linear RGD or iRGD, MBD represents a metal-ion binding domain comprising a bifunctional chelating agent and Pu is a polymeric unit. The present invention provides a novel radiotheranostic platform suitable for use as diagnostic or imaging agents or therapeutic agent.

This invention discloses an Evans blue-modified nucleic acid aptamer targeting EpCAM, its preparation method, and its application. The Evans blue-modified nucleic acid aptamer EB-SYL3C is composed of SYL3C, a bifunctional chelating agent, and truncated Evans blue. Using EB-SYL3C as a ligand can prolong the blood circulation half-life of SYL3C, as well as improve tumor uptake and tumor retention time, thereby enabling its application in EpCAM-targeted radionuclide diagnosis or treatment.

This invention relates to the field of nuclear medicine technology, and more particularly to a linker, compound, and radionuclide conjugate targeting prostate-specific membrane antigen (PSMA), and their applications. By linking a linker with a specific structure to a targeting carrier and a targeting ligand, respectively, a compound targeting PSMA is formed, and further labeled with a radionuclide to prepare a radionuclide conjugate. The linker in this invention can effectively enhance the affinity of PSMA ligands, and compounds including these linkers can serve as bifunctional chelating agents, simultaneously enabling the labeling of diagnostic and therapeutic radionuclides, achieving integrated diagnosis and treatment. Furthermore, the radionuclide conjugates constructed from these linkers exhibit good metabolic activity and significantly improved structural stability.

This invention discloses a polypeptide PET probe targeting FDG-negative solid tumors, its preparation method, and its application. It belongs to the fields of tumor diagnosis and nuclear medicine imaging. The polypeptide probe primarily targets the CD44v6 protein, as tumors with low FDG uptake often highly express this important target. Specifically, the bifunctional chelating agent NOA is linked to the optimized targeting polypeptide sequence NRWHEDC, and then radioactive nuclide is used for further processing. 18 F or 68 The Ga labeling and purification steps yielded a radionuclide-labeled peptide probe. This probe preparation method is simple and efficient, suitable for large-scale production. More importantly, it possesses high affinity and specificity, enabling PET to identify FDG-negative solid tumors, facilitating early detection, staging, efficacy evaluation, and recurrence monitoring.

Provided herein are bifunctional chelator compounds comprising a cyclic chelator moiety (e.g., 3,6,9,15- tetraazabicyclo-[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-acetic acid (PCTA)) and a linker moiety, wherein the linker moiety comprises a terminal squaramate moiety and a Ce-w aryl ring (e.g., a phenyl ring), a click reactive group (e.g., an alkyne, an azide, or a tetrazine), or both. Also provided are radiopharmaceuticals comprising a targeting moiety (e.g., an antibody), a bifunctional chelating linker having the structure of the bifunctional chelator compounds disclosed herein, and a radioactive isotope. Further disclosed are methods of making the bifunctional chelator compounds and radiopharmaceuticals, and their use in the diagnosis and treatment of diseases (e.g., cancer).

This invention discloses a radiopharmaceutical targeting chondroitin sulfate proteoglycan 4 (CSPG4) with a linear polypeptide and its preparation method. The radiopharmaceutical comprises a CSPG4-targeting polypeptide, a radionuclide, and a bifunctional chelating agent. The radionuclide is labeled with the CSPG4-targeting polypeptide by the bifunctional chelating agent, wherein the targeting polypeptide has a linear structure consisting of 10 or 11 amino acids. This series of radiopharmaceuticals can achieve specific nuclear medicine positron emission tomography (PET) or single-photon emission computed tomography (SPECT) imaging diagnosis of CSPG4-positive lesions, such as tumors, autoimmune diseases, cardiovascular diseases, and neurodegenerative diseases, in vivo.

Provided herein are bifunctional chelator compounds comprising a cyclic chelator moiety (e.g., 3,6,9,15- tetraazabicyclo-[9.3.1]pentadeca-1(15),11,13-triene-3,6,9-acetic acid (PCTA)) and a linker moiety, wherein the linker moiety comprises a terminal squaramate moiety and a C6-10 aryl ring (e.g., a phenyl ring), a click reactive group (e.g., an alkyne, an azide, or a tetrazine), or both. Also provided are radiopharmaceuticals comprising a targeting moiety (e.g., an antibody), a bifunctional chelating linker having the structure of the bifunctional chelator compounds disclosed herein, and a radioactive isotope. Further disclosed are methods of making the bifunctional chelator compounds and radiopharmaceuticals, and their use in the diagnosis and treatment of diseases (e.g., cancer).

Provided are a Nectin-4-targeting bicyclic peptide nuclide ligand and probe, a preparation method therefor, and a use thereof. The bicyclic peptide nuclide ligand and the bicyclic peptide nuclide probe are used for the imaging diagnosis of a Nectin-4-positive tumor patient and can achieve medication guidance for a patient receiving treatment with an anti-cancer targeted drug and real-time efficacy monitoring. A pharmacokinetic modification molecular polysarcosine is added between a chelating agent for radionuclide labeling and a Nectin-4-targeting polypeptide, thereby improving the biocompatibility of the probe and optimizing pharmacokinetic properties, especially non-tumor tissue clearance kinetics, so as to achieve better diagnosis and treatment effects. In the bicyclic peptide nuclide ligand DOTA-Sar-bicyclic peptide, DOTA is used as a bifunctional chelating agent, thereby achieving better in vivo and in vitro stability.

The invention belongs to the technical field of biological medicine, and particularly relates to a preparation for osteosarcoma diagnosis and / or treatment and a preparation method and application thereof, and the preparation is obtained by coupling CS polypeptide and a bifunctional chelating agent and then chelating gadolinium; the amino acid sequence of the CS polypeptide is as shown in SEQ ID NO. 1. The preparation provided by the invention can specifically target osteosarcoma, can also realize visual MR imaging of osteosarcoma focuses, and realizes neutron capture therapy and common photon sensitization therapy of osteosarcoma, namely diagnosis and treatment integration. The preparation has the advantages of being high in treatment specificity, remarkable in effect and small in damaged normal tissue, is a new treatment mode with good clinical application prospects, and is expected to finally improve prognosis of osteosarcoma patients.

The invention discloses a bifunctional chelating agent, a PSMA ligand compound thereof, a radiolabeled compound and application thereof, and relates to the technical field of radiopharmaceuticals. Wherein the structure of the bifunctional chelating agent is shown in the specification, and R is targeted peptide. The bifunctional chelating agent can form a stable complex with various radionuclides such as 68Ga, Al18F, 177Lu and the like, so that the bifunctional chelating agent can be applied to integrated tumor diagnosis and treatment of 68Ga / Al18F / 177Lu. The PSMA ligand compound based on the bifunctional chelating agent has good PSMA binding capacity, and compared with a tracer agent or a therapeutic agent in the prior art, a radiolabeled compound composed of the PSMA ligand compound and radionuclide has equivalent or even higher uptake value on tumors expressed by a prostate specific membrane antigen receptor, so that the PSMA ligand compound can be used for preparing a prostate specific membrane antigen receptor. In addition, the in-vivo inhibition effect is remarkable, and a new strategy is provided for diagnosis and treatment of tumors with prostate specific membrane antigen receptor expression.

The invention relates to the field of medicinal chemistry, in particular to a chelating agent with double connexons for coupling drugs and a preparation method of the chelating agent. The invention relates to a chelating agent with double linkers for coupling drugs. The chelating agent comprises a chelating agent body, an end A and an end B, wherein the end A and the end B are constructed on the chelating agent body; the end A is activated carboxyl-COOR *; and the terminal B is primary amine or secondary amine protected by Fmoc. According to the chelating agent with the double linkers, modular splicing is completed on the premise that a long linker is not additionally introduced, and the problems that synthesis steps are increased, positioning is uncertain, hydrophobicity is improved, and heterogeneity / inter-batch difference of products is increased when an existing common bifunctional chelating agent is introduced with an additional linker or a chelating agent is secondarily modified are solved.