110 results about "DOTA" patented technology

The invention relates to a radionuclide-labeled glucose derivative molecular probe and application thereof, and belongs to the technical field of nuclear medicine. According to the present invention, propargyl glycine is used to synthesize an amino acid skeleton, and the amino acid skeleton reacts with glucose azide to prepare a series of radionuclide-labeled glucose derivative molecular probes, such as [68Ga] Ga-NOTA-SDG, [68Ga] Ga-NOTA-DDG, [68Ga] Ga-NOTA-TDG, [68Ga] Ga-DOTA-SDG, [68Ga] Ga-DOTA-DDG and the like; the glucose derivative molecular probe labeled by the series of radionuclides has the advantages of being simple and rapid in labeling, high in radiolabeling yield and good in stability, can accurately position tumors, has good tumor uptake and lower non-target tissue uptake, and has great application prospects in preparation of broad-spectrum tumor imaging agents.

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 present disclosure relates to enriched and stable radiopharmaceutical compositions comprising [225Ac]Ac-DOTA-TATE.

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.

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.

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 belongs to the technical field of functional materials and membrane separation, and discloses a modified MXene piezoelectric ion screening membrane and preparation and application thereof, and a preparation method comprises the following steps: S1, preparing a two-dimensional MXene nanosheet dispersion liquid; and S2, adding a polydentate ligand into the mixture for modification, carrying out vacuum filtration, carrying out spin coating or blade coating on a porous substrate, and carrying out vacuum drying to obtain the modified MXene membrane. According to the preparation method, a bionic strategy is combined with piezoelectric characteristics of a material, an MXene nanosheet is modified by polydentate ligand (such as DOTA, EDTA, PA or Cyclone) molecules, an anti-swelling sub-nano channel is constructed, a piezoelectric effect is activated by combining mechanical stimulation such as ultrasonic and stirring, a piezoelectric channel is formed, and the preparation method is applied to the field of membrane separation by utilizing electromigration and a staggered electric field mechanism. The technical problems of swelling, insufficient mechanical stability, lack of dynamic regulation and control capability and the like of a traditional membrane material can be effectively solved, and particularly, efficient selective screening of monovalent / divalent ions can be realized.

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 relates to a method for producing gadoteric acid meglumine using high-purity tetraracetam (DOTA). This method does not require the use of organic solvents and optimizes synthesis process conditions. The synthesis process for producing gadoteric acid meglumine using tetraracetam includes at least one electrodialysis purification step. This step can produce tetraracetam and gadoteric acid meglumine with minimal impurity content.

The invention belongs to the field of nuclear medicine radiopharmaceuticals and relates to a double-target targeted polypeptide compound as well as a preparation method and application thereof. The structure of the compound or the pharmaceutically acceptable salt thereof comprises a TATE cyclic peptide structure, an FAPI-46 structure and a DOTA complexing group, wherein DOTA is used for complexing radionuclide; the DOTA complexing group is connected with two symmetrical phenylalanine through pentanic acid, so that the fat solubility of the DOTA complexing group is improved; the phenylalanine is respectively connected with the FAPI-46 and the TATE through the two hexanes, so that the steric hindrance of the FAPI-46 and the TATE is reduced. A radiopharmaceutical prepared from the double-target targeted polypeptide compound can be simultaneously combined with two targets, namely a somatostatin receptor and a fibroblast active protein, and has higher receptor binding affinity and higher tumor uptake through adjustment of lipid solubility and steric hindrance. Development of tumor-bearing animals shows that on SSTR2 / FAP < + > double-expression-bearing tumors, the double-target polypeptide drug is 4.8 times that of single-target TATE and 7 times that of single-target FAPI.

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 nuclear magnetic resonance imaging contrast agent GH-Gd as well as a preparation method and application thereof, and belongs to the multidisciplinary crossing fields of material science, kidney pathology, medical imaging and the like. The structure of the contrast agent GH-Gd is shown in the following formula, and the preparation method of the contrast agent GH-Gd comprises the following steps: adding a compound H-DOTA, GGT-1 and cesium carbonate into anhydrous acetonitrile, and carrying out heating reflux reaction to obtain a compound GH-DOTA; and carrying out chelation reaction on the compound GH-DOTA and gadolinium chloride to obtain the nuclear magnetic resonance imaging contrast agent GH-Gd. The contrast agent GH-Gd is formed by chelating a ligand GH-DOTA with Gd < 3 + >, the contrast agent sequentially plays three functions of kidney integration glomerular filtration, GGT and MPO programmed activated kidney enrichment and enzymatic hydrolysis kidney clearance, and the content and dynamic distribution information of GGT and MPO can be obtained while kidney injury is avoided. # imgabs0 #

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.