35 results about "Bifunctional chelator" patented technology

The invention provides a preparation method and application of a CD70 specific nano antibody molecular imaging probe. The probe comprises a tumor targeting group, radionuclide and a bifunctional chelating agent, the tumor targeting group is a CD70 specific nano antibody; the CD70 specific nano antibody is R8B4, and the amino acid sequence of the R8B4 is as shown in SEQ ID No. 1. The probe provided by the invention can realize noninvasive diagnosis of solid tumors such as renal clear cell carcinoma and malignant tumors of a blood system; reabsorption of the compound in the kidney is effectively inhibited through charge adjustment, kidney uptake is remarkably reduced, non-specific signals are reduced, the signal-to-noise ratio during targeted imaging or treatment is increased, and the imaging quality and treatment safety are improved. The probe not only has a wide application prospect in tumor diagnosis, but also provides a new technical support for targeted therapy and individualized precision medical treatment, and has important scientific research and clinical application values.

The invention belongs to the technical field of nuclear medicine molecular diagnosis and treatment, and discloses a modified CAIX targeting cyclic peptide and a nuclide marker and application thereof. According to the CAIX targeted cyclic peptide, a rigid bifunctional chelating agent RESCA is introduced to replace a traditional chelating agent, and a sulfonated or alkylated amino acid connector is combined, so that the enzymolysis resistance and in-vivo stability of the probe are remarkably improved. By optimizing the structure of the connector, the lipophilicity is reduced, liver and gall metabolism and non-specific uptake are reduced, and the high uptake rate of tumor target tissues is maintained. The cyclic peptide can label a diagnostic nuclide for PET imaging, or a therapeutic nuclide for intra-tumor irradiation therapy, using DOTA or NOTA in combination with an alkylated amino acid linker or an albumin ligand. Experiments show that the marker has high radiochemical purity, excellent pharmacokinetic characteristics and low kidney retention, and is suitable for precise diagnosis and targeted therapy of CAIX high expression tumors such as kidney cancer, colorectal cancer and brain glioma.

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.

The invention discloses a CXCR4 targeted nuclide diagnosis and treatment integrated probe as well as a preparation method and application thereof, idoCPCR4 is taken as a core targeting structure, a linker L1 containing positive charges is introduced between a bifunctional chelating agent and the idoCPCR4, a novel CXCR4 targeted ligand is prepared, and then a radiolabeled complex is prepared by labeling nuclide. Experimental results show that the affinity of the novel ligand to CXCR4 is remarkably enhanced, and the novel ligand is expected to be applied to CXCR4 targeted nuclide diagnosis and treatment.

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 present invention provides a CD70-specific nanoantibody, a molecular imaging probe, and a preparation method and application thereof. The probe includes a tumor-targeting group, a radionuclide, and a bifunctional chelator; the tumor-targeting group is a CD70-specific nanoantibody; the CD70-specific nanoantibody is RD06, and the amino acid sequence of RD06 is shown in SEQ ID No. 1. The probe of the present invention can achieve non-invasive diagnosis of solid tumors such as renal clear cell carcinoma and hematological malignancies; and through charge adjustment, it effectively inhibits its reabsorption in the kidney, significantly reduces renal uptake, reduces nonspecific signals, improves the signal-to-noise ratio during targeted imaging or treatment, and improves imaging quality and treatment safety. This probe not only has broad application prospects in tumor diagnosis, but also provides new technical support for targeted therapy and personalized precision medicine, and has important scientific research and clinical application value.

The invention relates to a low-pH insertion type compound targeting PSMA as well as a preparation method and application of the low-pH insertion type compound. The existing PSMA targeting probe has the problems of low tumor uptake and short residence time. The invention provides a low-pH insertion type compound targeting PSMA, which is formed by connecting a PSMA targeting group, a low-pH insertion group and a bifunctional chelating agent, and provides a low-pH insertion type radiolabeled complex targeting PSMA, which is used for preparing a human or animal tumor radiodiagnosis probe or treatment probe. The brand-new PSMA targeting probe is designed by adopting a mode of combining PSMA targeting small molecules with the low-pH insertion peptide, the uptake and retention of the PSMA targeting small molecules in tumors are improved by utilizing the anchoring characteristic of the low-pH insertion peptide in a cell membrane, and the PSMA targeting probe has proper physicochemical and radiology properties and relatively ideal biological characteristics and can be used for radiodiagnosis or treatment of tumors.

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 belongs to the field of radiopharmaceuticals and nuclear medicine, and relates to an MUC1 protein targeted nuclide probe system and application. The system comprises an MUC1 antibody and radionuclide, the radionuclide is labeled on the MUC1 antibody directly or through a bifunctional chelating agent, or the radionuclide realizes the labeling of the MUC1 antibody through a biological orthogonal system. The probe provided by the invention can be used for detecting or visualizing MUC1 protein, diagnosing individuals with MUC1 related diseases and screening people who may respond to MUC1 targeted therapy, and can also be used for differential diagnosis and staging of the MUC1 related diseases and malignant tumors, accurate positioning of focuses, curative effect monitoring and treatment.

The present invention belongs to the field of nuclear medicine molecular diagnosis and treatment technology, and discloses a modified CAIX-targeting cyclic peptide and its radionuclide label and application. The CAIX-targeting cyclic peptide significantly improves the probe's resistance to enzymatic degradation and in vivo stability by introducing a rigid bifunctional chelator, RESCA, in place of a traditional chelator, combined with a sulfonated or alkylated amino acid linker. By optimizing the linker structure, lipophilicity is reduced, liver and gallbladder metabolism and nonspecific uptake are reduced, and a high uptake rate in the tumor target tissue is maintained. The cyclic peptide can be labeled with diagnostic radionuclides for PET imaging, or therapeutic radionuclides for intratumoral irradiation therapy, using DOTA or NOTA in combination with an alkylated amino acid linker or an albumin ligand. Experiments have shown that the label has high radiochemical purity, excellent pharmacokinetic properties, and low renal retention, making it suitable for the precise diagnosis and targeted treatment of CAIX-high-expressing tumors such as renal cancer, colorectal cancer, and brain gliomas.

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.

The present invention provides a preparation method and application of a CD70-specific nano-antibody molecular imaging probe, wherein the probe includes a tumor-targeting group, a radionuclide, and a bifunctional chelator; the tumor-targeting group is a CD70-specific nano-antibody; the CD70-specific nano-antibody is R8B4, and the amino acid sequence of R8B4 is shown in SEQ ID No. 1. The probe of the present invention can realize non-invasive diagnosis of solid tumors such as renal clear cell carcinoma and hematological malignancies; and through charge adjustment, it effectively inhibits its reabsorption in the kidney, significantly reduces renal uptake, reduces nonspecific signals, improves the signal-to-noise ratio during targeted imaging or treatment, and improves imaging quality and treatment safety. This probe not only has broad application prospects in tumor diagnosis, but also provides new technical support for targeted therapy and personalized precision medicine, and has important scientific research and clinical application value.

The invention relates to a radionuclide labeled polypeptide targeting CD9, a preparation method and application, and belongs to the technical field of radioactive medicine. A radionuclide 177Lu is used for labeling a polypeptide specifically targeting CD9 through a difunctional chelating agent DOTA, a maleimide group is used for modification, the radionuclide labeled polypeptide is prepared, the radionuclide binding rate of the radionuclide labeled polypeptide is larger than 95%, and the radionuclide labeled polypeptide has high biological safety and stability, can be efficiently combined with serum albumin, and can be used for preparing the serum albumin labeled polypeptide. Mouse in-vivo experiments prove that the compound specifically targets tumor parts, can be applied to preparation of diagnosis or imaging reagents for glioblastoma, can also remarkably inhibit growth of tumors in mice, and has a positive treatment effect.

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).

The application discloses a kind of for PD-L1 targeted cyclic polypeptide radiopharmaceutical and preparation method thereof.The radiopharmaceutical is radionuclide-bifunctional chelator-PDLC6, polypeptide is labeled by bifunctional chelator through radionuclide, PDLC6 polypeptide is 12 amino acids composition, and 6-membered cyclic structure is formed by disulfide bond condensation, the radiopharmaceutical is realized to PD-L1 positive tumor or PD-L1 positive lesion, for example, the specific nuclear medical positron emission computed tomography (PET) imaging diagnosis of cardiovascular and cerebrovascular disease, trauma, autoimmune disease, and liver and lung fibrosis etc., through the specific recognition of cyclic peptide PDLC6 to PD-L1.

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.