83 results about "DOTA" patented technology

The invention belongs to the technical field of nuclear medicine molecular diagnosis and treatment, and discloses a modified CAIX targeting cyclic peptide, a nuclide marker and application of the modified CAIX targeting cyclic peptide in tumor diagnosis and treatment. 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 therapeutic nuclide marker of the cyclopeptide can be used for intratumoral 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 invention discloses a radionuclide-labeled collagen hybrid peptide probe as well as a preparation method and application thereof. The chemical structural general formula of the radionuclide-labeled collagen hybrid peptide probe is (metal nuclide-chelating agent)-Linker-CHP, wherein the metal nuclide is selected from any one of Al18F, 64Cu, 67Cu, 67Ga, 68Ga, 99mTc, 89Zr, 111In, 177Lu, 186Re and 225Ac, and the metal nuclide is selected from any one of Al18F, 64Cu, 67Cu, 67Ga, 68Ga, 99mTc, 89Zr, 111In, the chelating agent is selected from any one of NODAGA, NOTA2 and DOTA; linker is a connecting joint, and CHP is a collagen hybrid peptide with a polypeptide sequence of (GfO) n or (GPO) n. The probe not only has the characteristic of radiochemical marking stability, but also has the excellent biological distribution characteristics of high uptake in target organs such as tumors and low uptake in non-target organs such as liver and kidney, and has a good clinical application prospect.

The invention discloses a highly inert Gd-DOTA-based contrast agent with a hydrophobic side chain as well as a preparation method and application of the highly inert Gd-DOTA-based contrast agent, and two novel Gd-DOTA-based contrast agents Gd-L1 and Gd-L2 are successfully developed by respectively connecting hydrophobic 3-phenyl propylamine and 3, 3-diphenyl propylamine to Gd-DOTABA. The two novel Gd-DOTA-based contrast agents remarkably improve the chemical inertness of the complex, the dissociation half-life period of the complex in a 1 M HCl solution at 37 DEG C is about 5 times that of Gd-DOTA, and a powerful guarantee is provided for clinical safety; the MRI (Magnetic Resonance Imaging) performance of the liver in a mouse shows that Gd-L1 is equivalent to commercially available Gd-BOPTA and is suitable for imaging of a liver and gall system; after the Gd-L2 is combined with the human serum albumin, the longitudinal relaxation rate is obviously increased (r1 = 14.8 mM <-1 > s <-1 >, 1.4 T, 37 DEG C), the blood elimination half-life period in a rabbit model is about 18 minutes, and the Gd-L2 is suitable for vascular MRI (Magnetic Resonance Imaging). The two contrast agents avoid the spleen residual problem, the organ accumulation possibility is reduced, and a safer and more efficient MRI diagnostic tool is provided for clinic.

The invention provides an Olaparib derivative as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The Olaparib derivative is a compound as shown in a formula (A) or a derivative thereof, and the structural formula of the compound as shown in the formula (A) is # imgabs0 #; wherein R is equal to # imgabs 1 # or # imgabs 2 #. The compound, the preparation method and the application have the advantages that the designed compound is high in tumor uptake, low in normal tissue uptake and low in target-to-non-target ratio, so that the property of [68Ga] DOTA-Olaparib is greatly improved, and accurate outlining of tumors is facilitated. Meanwhile, the compound provided by the invention has strong chelating ability, and can form a stable chelate with most radioactive metals, thereby facilitating the integration of tumor diagnosis and treatment.

Provided in the present invention are a monosubstituted cyclic ligand, and a preparation method therefor and a use thereof, and a monosubstituted cyclic rare earth complex, and a preparation method therefor and a use thereof, relating to the technical field of contrast agents. The monosubstituted cyclic ligand uses the ring structure of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid as a parent ring, and an R-modified tyrosine group increases the structural rigidity of the parent ring and improves the stability of the complex. Direct introduction of benzyloxy-, ethoxy- or hydroxy-substituted benzyl substituents on the carbon atoms of the DOTA ring maintains the original eight-coordination structure, and improves the relaxation rate of the complex, in addition to increasing the stability of the complex. Compared with Gd-DOTA, both the kinetic inertia and the relaxation rate are improved. The complex formed by the ligand and Gd(III) or Eu(III) is highly stable, and has strong specificity for the liver or for inflammation, and causes no obvious damage to the heart, the liver, the spleen, the lungs or the kidneys.

The invention relates to the technical field of environmental catalysis and pollution treatment, in particular to a chelated iron desulfurizer. According to the desulfurizer, DOTA is used as a core chelating agent, an iron active center is accurately anchored to a shell layer of a polymer core-shell structure microsphere through a multi-step polymerization and functionalization process, and the design of solution-state complexing iron is assisted, so that the desulfurizer has both solid-phase localization and solution compensation, the capability of resisting poisoning of impurities such as cyanide and mercaptan is remarkably improved, and iron loss is reduced. The desulfurizer is high in desulfurization efficiency and large in sulfur capacity, can stably operate for a long period, shows excellent continuous activity and selectivity under the conditions of coexistence of various impurities and repeated regeneration, and has a good application prospect.

The invention discloses a PET (positron emission tomography) imaging agent, a precursor and a probe for targeting an EphA2 receptor as well as a preparation method and application of the PET imaging agent, the precursor and the probe, and a radioactive probe which is formed by labeling a chelating agent (such as DOTA and NOTA) and a radionuclide (such as 68Ga) by taking bicyclic peptide as a targeting group is specifically combined with the EphA2 receptor highly expressed on the surface of a tumor cell. According to the invention, a conformation limitation strategy is adopted for transforming the peptide probe targeting EphA2 for the first time, the bicyclic peptide radioactive probe with excellent targeting performance and in-vivo imaging effect is obtained, the tumor uptake value is high, and tumor and non-tumor imaging is clear; and successful imaging in a fibrosarcoma model. According to the EphA2 receptor-targeted PET imaging agent provided by the invention, the precursor, namely the probe, has the advantages of simplicity in preparation, good targeting property, excellent imaging effect and the like, can be used for PET imaging diagnosis, prognosis evaluation and targeted therapy guidance of EphA2 positive tumors, and has good clinical value.

The invention provides a molecular probe targeting EDB-FN as well as a preparation method and application of the molecular probe. The structural formula of the molecular probe targeting EDB-FN is shown in the specification, according to the molecular probe targeting EDB-FN, the probe is based on a cyclic peptide probe with Lys-Glu side chain lactam bridge conformation fixed, the connection mode of a DOTA chelating agent is optimized, and the clinical transformation bottlenecks that an existing probe is poor in stability, low in affinity, insufficient in targeting specificity, poor in diagnosis and treatment integration compatibility and the like are solved. The probe can be used for early diagnosis and molecular imaging research of tumors, and provides a reliable basis for tumor malignancy degree evaluation and treatment effect monitoring.

The present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel DOTA-haptens that may be complexed with a radioisotope (e.g., 225Ac). Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

The present invention provides a combination of two or more imaging agent conjugates comprising an imaging agent conjugated to a targeting ligand, wherein the imaging agent comprises one or more of: ZW800-1, ZW830-1, ZW700-1-Forte, ZW-DOTA, ZW-PyC3A, ZW-Macropa, ZW-Porphyrin, ZW-NOTA, and ZW-Deferoxamine; and the targeting ligand comprises one or more of: cRGD, dPSMA-617 or KUE, FAP, Bombesin Receptor Binding Vector, or Octreotide Binding Vector, or one or more of the peptides selected from SEQ ID Nos: 1 to 4.

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 present disclosure provides compositions and methods for the detection and treatment of cancer. Specifically, the compositions of the present technology include novel compounds that may be complexed with a radioisotope. Also disclosed herein are methods of the using the DOTA-haptens of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

The invention discloses a double-target small-molecule probe, a radionuclide-labeled double-target small-molecule probe as well as a preparation method and application of the radionuclide-labeled double-target small-molecule probe. The medicine < 68 > Ga-DOTA-PRE / RGD is obtained by labeling < 68 > Ga radionuclide, and is applied to PET / MR (positron emission tomography / magnetic resonance imaging) imaging of pancreatic cancer tumors. A radioactive product with high purity and high stability (greater than 93%) is obtained through a simple marking method; the obtained double-target radioactive small molecular probe 68Ga-DOTA-PRE / RGD has a huge potential for the accurate diagnosis of pancreatic cancer.

The present application relates to the field of environmental catalysis and pollution control technology, and particularly relates to a chelated iron desulfurizer. The desulfurizer takes DOTA as a core chelating agent, and through a multi-step polymerization and functionalization process, the iron active center is precisely anchored in the shell layer of the polymer core-shell structure microsphere, supplemented by the design of solution-state complex iron, which has both solid-phase localization and solution compensation, significantly improving the resistance to cyanide, mercaptan and other impurities poisoning capacity, and reducing iron loss. The desulfurizer has high desulfurization efficiency, large sulfur capacity, and can be stably operated for a long period. Under the conditions of coexistence of various impurities and repeated regeneration, the desulfurizer shows excellent sustained activity and selectivity, and has good application prospect.

The present disclosure provides a cyclic Gd (III) complex with a chemical structure shown in formula I, where a ring structure of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is used as a parent ring, lipophilic groups R′ and R″ in formula I are respectively introduced to a α-position of phenylacetic acid (PAA) and a benzene ring structure, and a chiral group R in formula I is introduced to a DOTA macrocycle position. The chiral group R can increase the rigidity of a macrocyclic structure and improve the stability of the complex, and the lipophilic groups R′ and R″ can bind to hepatocellular organic anion transporting polypeptides (OATPs), thereby greatly improving the distribution of the cyclic Gd (III) complex as a contrast agent in the liver and gallbladder, that is, thereby providing excellent targetability.

The present application relates to the field of biological medicine, and provide a kind of targeting PSMA dimer compound and its derivative and application, the structure general formula of the dimer compound is as shown in formula (I).The dimer compound and its derivative of the present application have very high affinity and targeting to PSMA, after being labeled with suitable radionuclide, can be used as nuclear medicine molecular probe, to realize early diagnosis, staging and treatment of prostate cancer, 68 Ga]diPSMA-1-DOTA showed good tumor uptake in PET imaging of tumor mice.Therefore, this kind of radioactive complex has good clinical application prospect in tumor imaging targeting PSMA (especially PET imaging), and lays an important foundation for the radiotherapy application of [ 177 Lu]diPSMA-1-DOTA and [ 225 Ac]diPSMA-1-DOTA.

The invention discloses a novel nuclear magnetic resonance contrast agent Gd-DOTA-PP for targeting citrullinated histone to achieve neutrophil extracellular trap net imaging and a preparation method and application thereof.The method comprises the steps that citrullinated histone targeting polypeptide PP and ligand molecules DOTA-NHS are combined, and a compound DOTA-PP is obtained; and then gadolinium (Gd) ions are introduced into the DOTA-PP through a coordination reaction, and the novel contrast agent Gd-DOTA-PP is prepared. The contrast agent can be selectively combined with an important marker, namely citrullinated histone, of neutrophil extracellular trapping nets (NETs), and T1 weighted imaging signals of a target area are remarkably enhanced. The preparation method is simple and convenient to operate, the preparation process is highly controllable, and the obtained contrast agent has excellent biocompatibility and targeting characteristic. The accurate targeting ability of the probe enables the influence signal of the probe in NETs enrichment areas such as tumor early metastasis, tumor infiltration lymph nodes and the like to be obviously enhanced, a powerful tool is provided for tumor diagnosis, especially accurate diagnosis of the early metastasis, and the probe has important clinical application value.

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 belongs to the technical field of nuclear medicine, and particularly relates to a PARP inhibitor, a radionuclide marker thereof, a preparation method and application. One purpose of the present invention is to provide a PARP inhibitor, which is a compound represented by a formula I or a salt thereof, and the structure of the compound represented by the formula I is shown in the specification. According to the technical scheme, diagnostic radionuclide (such as 68Ga) and therapeutic radionuclide (such as 177Lu) are compatible through optimal design of the precursor. The advantages fully show that the radionuclide-labeled DOTA-nirapalide has good feasibility and application potential in the aspect of tumor diagnosis and treatment integration.

Described herein are multi-specific binding agents that bind A33 and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid. Also provided herein are methods of using multi-specific binding agents or compositions thereof for the detection, prevention, and / or therapeutic treatment of diseases characterized by expression of the A33 glycoprotein antigen, in particular, colorectal cancer.

The invention discloses a nuclide-labeled compound targeting PSMA-TATE double targets as well as a preparation method and application of the nuclide-labeled compound. The nuclide-labeled compound is DOTA-PSMA-TATE labeled by < 68 > Ga or < 177 > Lu. The < 68 > Ga and < 177 > Lu labeled PSMA-TATE targeted double-target tumor developer provided by the invention is stable in property and good in imaging effect, and has high affinity and specificity to PSMA and TATE, and further preclinical animal experiment research proves that < 68 > Ga-DOTA-PSMA-TATE is expected to become a broad-spectrum tumor developer with a good application prospect, and < 177 > Lu-DOTA-PSMA-TATE is expected to become a treatment means.

The application provides a gadoterate derivative, a preparation method and application thereof, and belongs to the technical field of medicines.The application provides a gadoterate derivative with a structure shown in formula I-1 or formula I-2, and the application uses a sulfonamide compound and an amine glucose as a targeting molecule, designs a contrast agent for targeting tumors on the basis of a chiral gadoterate (Gd-DOTA) compound, and the specific contrast effect for tumors is excellent.The test results show that the gadoterate derivative has excellent targeting property for breast cancer cells.

Disclosed in the present invention are a radiolabeled compound of a risedronic acid derivative, and a precursor compound thereof, and a preparation method therefor and the use, which belong to the technical field of nuclear medicine. Provided in the present invention are a precursor compound of a radiolabeled compound of a risedronic acid derivative as shown in formula (I) or a pharmaceutically acceptable salt thereof, and a radiolabeled compound of a risedronic acid derivative as shown in formula (II) or a pharmaceutically acceptable salt thereof. In the present invention, risedronic acid is creatively combined with a chelating agent to obtain NOTA-risedronic acid and DOTA-risedronic acid, and then a radionuclide is used for labelling. The radiolabeled product of the present invention has a relatively high water solubility, good in-vitro stability at room temperature, and a high plasma protein binding rate, and exhibits a relatively high and prolonged bone uptake in terms of imaging and in vivo distribution in mice; and compared to 68Ga-DOTA-ibandronic acid, the uptake of the compound of the present invention at the lesion site is twice as high.

The present invention provides a combination of two or more imaging agent conjugates comprising an imaging agent conjugated to a targeting ligand, wherein the imaging agent comprises one or more of ZW800-1, ZW830-1, ZW700-1-Forte, ZW-DOTA, ZW-PyC3A, ZW-Macropa, ZW-porphyrin, ZW-NOTA, and ZW-Deferoxamine; and the targeting ligand comprises one or more of a cRGD, a dPSMA-617 or a KUE, a FAP, a bombesin receptor binding vector, or a octreotide binding vector, or one or more of peptides selected from SEQ ID No: 1-4.

The application discloses a novel radionuclide therapeutic drug targeting nucleolus DDX24 helicase and a preparation method and application thereof. 64 The Cu-DOTA-TDP-2 has good tumor targeting uptake specificity, and is expected to provide a precise molecular imaging method for esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has high radiochemical yield and specific activity, good chemical stability, high affinity for DDX24 helicase, and a simple and easy-to-operate preparation method, and can be used for the treatment of DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has excellent biological safety performance and good tumor inhibition effect in esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors.

The present disclosure relates to concentrated and stable parenteral 177Lutetium-DOTA-TATE radionuclide complex solutions. Drug stability is achieved by the combination of from 5 mg / mL to 25 mg / mL of ascorbic acid or a salt thereof and from 1 v / v% to 3 v / v% ethanol.

The invention provides a sugar nucleic acid dual-targeting radioactive molecular probe for targeted therapy of bladder cancer as well as a preparation method and application of the sugar nucleic acid dual-targeting radioactive molecular probe, and belongs to the technical field of biological medicines. The probe is composed of an Sgc8 aptamer for recognizing bladder cancer cell PTK7 protein, three nitrine mannose molecules of a targeted M2 type macrophage CD206 receptor and a DOTA structure for chelating 177Lu, and precise assembly is achieved through a click chemical reaction and complementary base pairing. The probe has dual targeting ability, can act on bladder cancer cells and M2 type macrophages in a tumor microenvironment at the same time, significantly prolongs the retention time (gt, 48 hours) in the bladder, induces immune activation while killing tumor cells, and realizes the synergistic effect of radiotherapy and immunotherapy. The problems that an existing bladder cancer treatment probe is insufficient in targeting, poor in stability and limited in treatment effect are solved, a new strategy is provided for precise treatment of bladder cancer, and the bladder cancer probe has good clinical transformation value.

This application relates to the field of biomedical technology, specifically disclosing a therapeutic probe targeting neuroblastoma GD2, adapted to the clinical needs of relapsed, refractory, and high-risk neuroblastoma. This therapeutic probe comprises paired diagnostic and therapeutic components, both using the humanized anti-GD2 monoclonal antibody hu3F8 as the sole targeting carrier; the diagnostic component is a zirconium-89-labeled deferoxamine-hu3F8 conjugate, and the therapeutic component is an actinium-225-labeled DOTA-hu3F8 conjugate. This application also discloses its preparation method, obtaining a high-purity product through three steps: antibody-chelating agent conjugation, radionuclide labeling, and purification. This probe system can be used to prepare a therapeutic drug composition for neuroblastoma, exhibiting strong targeting specificity, enabling imaging-guided precise radioimmunotherapy, and demonstrating good synergistic diagnostic and therapeutic effects.

The present disclosure provides compositions and methods for the detection, and treatment of cancer. Specifically, the compositions of the present technology include multimodal fluorine-cyanine-DOTA-hapten compositions that may be complexed with a radioisotope (e.g., 175Lu). Also disclosed herein are methods of using the fluorine-cyanine-DOTA-hapten compositions of the present technology in diagnostic imaging as well as pretargeted radioimmunotherapy.

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.