52 results about "DOTA" patented technology

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.

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 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 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.

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.

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.

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.

The application discloses a PET tracer targeting carbonic anhydrase IX (CA IX) and a preparation method and application thereof. 68 The tracer is prepared from a DOTA-bis-sulfonamide precursor compound and GaCl3 reaction. The tracer has high hydrophilicity, excellent stability in vitro and in vivo, low uptake of non-target organs and is mainly excreted through the kidney. Micro-PET / CT imaging shows that the tumor uptake is linearly correlated with the CA IX protein expression level measured by immunohistochemistry. Acute toxicity experiments show that the tracer has good biological safety. The application further provides a radiopharmaceutical composition containing the tracer and application of the tracer in preparation of a PET imaging agent for diagnosing CA IX positive tumors. The tracer has the advantages of high labeling efficiency, low background interference, accurate quantification and potential integration of diagnosis and treatment, and is suitable for precise molecular imaging of CA IX high expression tumors such as clear cell renal cell carcinoma and colorectal cancer.

The invention discloses a high-affinity HER2 targeting polycyclic peptide molecule and a preparation method and application thereof.The preparation method comprises the steps that affinity optimization is conducted on initial HER2 targeting polycyclic peptides obtained through phage display library screening by combining a yeast display technology with an error-prone PCR directed evolution system, and a series of high-affinity disulfide bond-rich polycyclic peptides (DDMP) are obtained; the polycyclic peptide is coupled with a conjugate (DOTA or FITC) and a linker, so that a monovalent or divalent molecular probe can be constructed; the molecular probe has high specificity, high stability and good biocompatibility, can be used for accurate imaging and quantitative evaluation of HER2 positive cells / tumors and diagnosis and targeted therapy of HER2 signal path related diseases through radionuclide labeling or fluorescence labeling, and provides a novel tool and a transformation basis for early diagnosis and accurate treatment of HER2 positive solid tumors.

Provided herein are methods of treating somatostatin receptor-positive, estrogen receptor-positive, human epidermal growth factor receptor 2-negative breast cancer using 225Ac-DOTA-TATE or a pharmaceutically acceptable salt thereof.

The present invention discloses a PSMA-targeted radiometal complex containing a nitroaromatic heterocyclic group and its preparation, which belongs to the technical fields of radiopharmaceuticals and medical imaging. The general formula of the PSMA-targeted radiometal complex containing a nitroaromatic heterocyclic group of the present invention is shown in Formula I and Formula II. The present invention is the first to link both a nitroaromatic group and a PSMA-targeting group to a metal chelator (such as HBED-CC, DOTA, DOTA(GA)2, NOTA, AAZTA, etc.) and to target a radiometal nuclide, e.g. 68 Ga, 18 F-AlF, 177 Lu, 90 Y, 44 Sc, 225 Ac, 212 Pb, 213 The radioactive metal marker is labeled with Bi, etc. The synergistic effect of the nitroaromatic heterocyclic group in vivo is expected to increase the uptake of the radioactive metal marker by prostate cancer, promoting metabolism in non-target organs and improving the therapeutic efficacy of radiopharmaceuticals against tumors. JPEG2026508753000106.jpg2835JPEG2026508753000107.jpg2145 (wherein the R1 and R2 groups are nitroaromatic heterocyclic groups; L2 is a linking group between the R1 group and L1, where L1 is a linking group between the chelator and the structure PSMA targeting structure; L4 is a linking group between the R2 group and L3, where L3 is a linking group between the chelator and the structure PSMA targeting structure; and ChelatoR1 and ChelatoR2 are chelators or chelating structures.)

This invention provides a monosubstituted cyclic ligand, its preparation method, and its application, as well as a monosubstituted cyclic rare earth complex, its preparation method, and its application, relating to the field of contrast agent technology. The monosubstituted cyclic ligand provided by this invention uses a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid ring structure as the parent ring. The R-modified tyrosine group increases the rigidity of the parent ring structure and improves the stability of the complex. Benzyl substituents, ethoxy, or hydroxyl-substituted benzyl groups, are directly introduced onto the carbon atoms of the DOTA ring, maintaining the original eight-coordinate structure. This increases the stability of the complex while also improving its relaxation rate; both kinetic inertness and relaxation rate are improved compared to Gd-DOTA. The complexes formed by this ligand with Gd(III) or Eu(III) exhibit high stability and strong specificity for liver or inflammation, without significant damage to the heart, liver, spleen, lungs, or kidneys.

The invention provides a nuclide microneedle patch for treating scars and a preparation method of the nuclide microneedle patch. A needle body part of the microneedle patch comprises metal nuclides and DOTA molecules with photo-crosslinking activity, the DOTA molecules with photo-crosslinking activity are chelated with the metal nuclides and then can be prepared into the nuclide microneedle patch through ultraviolet light crosslinking curing, and the metal nuclides are uniformly distributed in the needle body. The nuclide microneedle patch can be directly adhered to a body surface scar part, metal nuclide is delivered into scar tissue cells for radiotherapy, the penetrating power of the metal nuclide to scars is improved, and the metal nuclide cannot be left in scar tissues after radiotherapy is finished. The nuclide microneedle patch provided by the invention is high in universality and good in stability, a new direction is provided for treating scars, and meanwhile, the uptake probability of normal tissues and organs to the metal nuclide is extremely low or almost no uptake.

The invention relates to a saturated alkyl double-chain modified magnetic resonance imaging contrast agent as well as a preparation method and application thereof, and belongs to the technical field of preparation of magnetic resonance imaging contrast agents. The contrast agent provided by the invention not only retains the high dynamic stability and low gadolinium leakage risk of an annular contrast agent, but also significantly improves the uptake rate of Gd-DOTA in the liver through introduction of saturated alkyl double chains, and effectively solves the problem of cytotoxicity possibly generated by long-chain single-chain modification. Animal experiment results show that the contrast agent provides a clear magnetic resonance imaging signal in a living body, and provides a clearer and more accurate image support for diagnosis of liver diseases by optimizing the length and the structure of an lipid chain. While the imaging effect is improved, the safety and stability of the contrast agent are ensured, and the contrast agent has a wide application prospect.