73 results about "DOTA" patented technology

A process for producing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) including salts and hydrates thereof of general formula (I) from the respective cyclen.

The process involves the use of cationic- and anionic exchange resins and solvent treatments to remove the organic and inorganic contaminants. Any cations present in the raw DOTA or other contaminants resulting from the reaction of cyclen are largely reduced in early stages of the process allowing to obtain good yields of DOTA in a purified grade and in an easier and reliable way. The process is useful for the production of DOTA, of macrocyclic compounds including metal ions complexes thereof and of compositions including the macrocyclic compounds that can be used as contrast agents for magnetic resonance imaging.

The invention discloses a magnetic nanometer material and application thereof to phosphopeptide enrichment. 4-carboxyphenyl porphyrin (TCPP) and 1,4,7,10-tetraazacycl ododecane-N,N,N,N-tetraacetate (DOTA) are in covalent linkage to the surface of an amino-modified magnetic nanometer material modified through ethanediamine, and lanthanide series metal ions are immobilized on the surface of the material to synthesize a novel magnetic nanometer material. The metal ion-modified magnetic nanometer material has higher selectivity, sensitivity and enrichment efficiency in the phosphopeptide enrichment process. Compared with the traditional TiO2 method, the metal ion-modified magnetic nanometer material has higher phosphopeptide enrichment specificity and selectivity.

The invention discloses a preparation method of heavy metal cadmium artificial antigen, which applies 2-S-(4- aminobenzene)-1, 4, 7, 10 tetraazacyclo cyclononane-1, 4, 7, 10-acetate tetrahydrate(p-NH2-Bn-DOTA, DOTA for short) as cheating agent, and couples cadmium ion chelating agent composite with carrier protein bovine serum albumin BSA or egg albumin OVA; thus the artificial antigen is prepared. The method adds the sodium borohydride processing step on the basis of traditional method, and improves the coupling efficiency and antiserum titre. The invention further discloses an application ofDOTA in preparation of the heavy metal cadmium artificial antigen.

The invention discloses a diagnosis and treatment integrated PSMA inhibitor, a compound and a preparation method and application thereof. The structure of the compound is shown as a formula A in the specification, wherein the R1 is DOTA or NODA used for complexing (radioactive) metal ions, radioactive metal nuclide is used for diagnosis or treatment, non-radioactive metal nuclide is used for being combined with radionuclide, and R2 is a coupling agent which is benzylamine, cyclohexylmethylamine or butylamine. The invention also provides a preparation method and application of the compound. The compound has very high affinity with prostate cancer specific membrane antigen (PSMA), and compared with existing PSMA treatment and imaging agents, the compound has the advantages that high swelling uptake is maintained, radioactive excretion of in-vivo non-target regions is accelerated, non-specific uptake of glands is reduced, and treatment and imaging of tumors are facilitated; and meanwhile, when the developing agent is marked by nuclide, the effect of integrating tumor diagnosis and treatment can be achieved, and the PSMA inhibitor is particularly suitable for treatment, diagnosis, staging and the like of prostate cancer.

The invention discloses a tumor PD-L1 targeting PET imaging agent as well as a labeled precursor, a preparation method and application thereof, and belongs to the technical field of radiopharmaceutical chemistry. The structure of a labeled precursor of the tumor PD-L1 targeting PET developer is shown as a formula I, and the structure of the tumor PD-L1 targeting PET developer is shown as a formula II. According to the invention, a bifunctional chelating agent DOTA and a cyclic peptide inhibitor SETSKSF are creatively connected together, and a labeled precursor of a PET imaging agent of a targeted tumor PD-L1 as shown in a formula I is synthesized. After the precursor compound is marked with Ga-68, a compound shown in a formula II can be obtained, and the compound has good stability, excellent pharmacokinetics, good binding specificity with tumor PD-L1 and easy synthesis.

The invention discloses a magnetic signal probe of a magnetic relaxation time immunosensor. The probe comprises a Gd < 3 + > chelate, polylysine and a superparamagnetic nano-particle of an antibody which are coupled. By coupling polylysine and an antibody to the surfaces of superparamagnetic nano-particles,the antibody-superparamagnetic nanoparticle-polylysine conjugate with the multi-dimensionalspace reticular dendritic structure is obtained; then, succinimide-tetraazacyclododecane tetraacetic acid with chelating performance is coupled to the surface of polylysine, and paramagnetic Gd < 3 +> ions are added; gd < 3 + > is captured through DOTA, and finally, a large number of Gd < 3 + > ions are chelated on the surfaces of the superparamagnetic nano-particles, so that the magnetic relaxation time immunosensing magnetic signal probe with multiple signal amplification is obtained. According to the invention, magnetic separation and magnetic sensing integrated nano magnetic particles andparamagnetic Gd < 3 + > ions are controllably assembled into the multifunctional nano magnetic probe for the first time, so that multiple amplification of sensing signals is realized, and the sensitivity and detection speed of the sensor are greatly improved.

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.

According to the invention, liquid nuclide < 18 > F-labeled FAPI (< 18 > F-FAPI) is fitted, specifically, the < 18 > F-FAPI with a relatively long half-life period is synthesized by utilizing a strong complexing and bridging effect of Al < 3 + > ions on < 18 > F ions and cyclic coordination groups (DOTA and NOTA), and a radiochemical purity synthesis process of the Al< 18 > F-FAPI of 99% or above and a single yield of more than 100 mCi are realized, so that clinical requirements are met.

The invention discloses a T1 strengthened nanometer magnetic contrast agent having the function of activating targeting properties of blood platelets and a preparation method of the T1 strengthened nanometer magnetic contrast agent belonging to the field of nuclear magnetic resonance contrast agents. The characteristics of "dissociation-self-assembly" and surface modificability of an apoferritin nanometer cage under different pH environment are utilized, paramagnetic Gd-DOTA is loaded into the apoferritin nanometer cage, ligand-KGDS tetrapeptide specifically targeting and activating the bloodplatelets is coupled to the surface of Gd-loaded apoferritin, and therefore, nanometer particles which can actively target and activate the blood platelets and have nuclear magnetic resonance T1 weighted imaging strengthened contrast effects can be obtained. The particle diameter of the nanometer contrast agent is about 10nm, the nanometer contrast agent has favorable contrast effects, targeting properties for activating the blood platelets, and biocompatibility; precise visualization of thrombosis is hopefully realized through targeting and activating the blood platelets, and more comprehensive molecule information is provided for early prevention, diagnosis and treatment of cardiovascular diseases.

The invention discloses a DZ-1-Lys-DOTA conjugate compounded with radioactive metal. The DZ-1-Lys-DOTA conjugate comprises a heptamethyl cyanine dye group coupled with a DOTA group through a lysine cross-linking agent, wherein the DOTA group is compounded with the radioactive metal M; the radioactive metal M adopts one or more radioactive metal groups of lutetium -177, yttrium -90 and gallium- 68; the invention also discloses application of the DZ-1-Lys-DOTA conjugate compounded with the radioactive metal. The DZ-1-Lys-DOTA conjugate comprises improved imaging, improved treatment, improved image-guided treatment, improved serum stability, improved penetrability of tumors (especially solid tumors) and/or affinity of therapeutic and diagnostic pairs. Through the scheme, the DZ-1-Lys-DOTA conjugate has very high practical value and popularization value in the technical field of the DZ-1-Lys-DOTA conjugate.

The invention discloses a rare-earth cage-like coordination compound metal fluorescent dual-mode label for flow cytometry, which is obtained by coupling a polymer with a rare-earth cage-like coordination compound as shown in the a formula (I-8) defined in the description with a monoclonal antibody, wherein Ln<3+> is a lanthanide rare earth metal ion. Different from an existing mass spectrum flow type polymer metal chelating label, a DOTA coordination group is ingeniously replaced with a cage-shaped coordination group, on the one hand, the coordination capacity of rare earth ions is improved, leakage of the rare earth ions can be reduced, and signals of the metal label in a flow type mass spectrum are stronger; on the other hand, due to the antenna effect of the cage-like coordination compound, the fluorescence intensity of the rare-earth coordination compound is greatly improved, and the rare-earth coordination compound can be detected by a flow cytometry. According to the invention, the rare earth cage-like coordination compound metal fluorescent dual-mode label for flow cytometry can be prepared at a lower cost, so that the use cost of a mass spectrum flow detection reagent can be greatly reduced.

Accordingly, embodiments herein disclose a compound and method of small molecule inhibitors or ligands for diagnosis and treatment of cancers such as prostate, brain, breast, etc., and neurodegenerative diseases. A new class of PSMA inhibitors called as aminoacetamide, 1, has been designed by extensive in silico studies. A simple, mild and high yielding synthetic methodology is developed for 1 and shown to have high affinity for PSMA protein. Fluorescent conjugates 22 and 25 derived from 1 show selective uptake in prostate cancer cell lines and can be used for surgical removal of tumors during intra-operative surgery. Conjugates 31 and 34 for tagging 99mTc radioisotope were synthesized. Macrocyclic chelating cores such as DOTA, NOTA or prosthetic groups can be introduced to tag radionuclides 68Ga, 64Cu, 18F and 177Lu for diagnosis and treatment of PCa, incurable mCRPC and neurodegenerative diseases such as ALS, schizophrenia and neuropathic pain that over-express PSMA protein.

The invention discloses a preparation method of DOTATATE. The method comprises the following specific steps of: sequentially coupling solid-phase carrier resin to amino acids, the N ends and side chains of which have protecting groups, according to the amino acid sequence of DOTATATE, and then, coupling DOTA(tBu)<3> so as to obtain linear peptide resin of DOTATATE; then, adding lysis solution to remove the protecting groups and cutting the resin to obtain linear peptide of DOTATATE; and finally, performing oxidization by using an oxidizing agent to obtain DOTATATE crude peptide. According to the preparation method in the invention, hydroxyl resin with easily available raw materials and low-price amino acids with side chain protection are adopted to synthesize the linear peptide resin; then, the linear peptide is cracked; the oxidizing agent easy to control is adopted to oxidize the linear peptide so as to obtain the target crude peptide; use of a highly toxic reagent is avoided; and finally, purification, salt conversion, concentration and drying are carried out, so that refined peptide is obtained. The method in the invention has the advantages of short synthesis route, easily controlled linear peptide quality, low synthesis cost, high yield and high finished product purity, and is suitable for large-scale production.

Methods and compositions for treating, diagnosing and staging cancers, in particular overexpressing the Human Epidermal growth factor Receptor 2 protein (HER2+) given rise to in breast, gastric, gastroesophageal, ovarian, pancreatic cancer and brain tumors, which may be metastatic to the brain or other site. More specifically, the invention provides for Targeted Radionuclide Therapy (TRNT) with a compound of the invention having a peptide that targets the HER2+ cells, a second component for combining metals into complexes through a ring structure (DOTA), and a third radioisotope component, Lu-177 and Ga-68, in which embodiments further include a companion diagnostic, and in which embodiments further include anti-integrin precision medicines for cancers expressing αvβ3 and αvβ5 integrins, HER2+, vascular endothelial growth factor, vitronectin, fibronectin, tenascin, reelin, kindlin and talin. TRNT may be administered alone or in combination with standard-of-care; an immunooncologic and/or chemotherapeutic, adjuvantly or neoadjuvantly.

The invention provides a preparation process and a purification process of gadadotec acid meglumine. The preparation process comprises the steps of adding purified DOTA into pure water, stirring and dissolving at room temperature, adding gadolinium oxide and microporous calcium silicate particles, adding meglumine until the pH value of the solution is 7-9, carrying out ultrasonic oscillation, filtering, heating the filtrate to the temperature of 40-50 DEG C, stirring, reacting for 2-4 hours, filtering the precipitate, and performing vacuum drying to obtain the product. The purification method provided by the invention comprises the steps of dissolving a crude product gadadotec acid meglumine in 100ml of methanol, heating while stirring until the gadadotec acid meglumine is dissolved, adding 50ml of water while stirring, stopping stirring, naturally cooling, slowly separating out fine crystals, cooling to the temperature of 5-10 DEG C after 3 hours, adding 30ml of water while stirring, stopping stirring after adding, standing for crystallization, and carrying out suction filtration on the separated white crystals, washing with a small amount of methanol, and carrying out vacuum drying at the temperature of 60 DEG C to obtain crystalline powder.

The present invention provides a novel method of removing gadolinium ions from a solution comprising gadolinium complexed with DOTA. The method of the present invention is relatively simple and cost effective compared to known methods.

The invention relates to the technical field of nano biological probes, in particular to a preparation method of a nano probe for nuclide imaging and multi-mode combined treatment. A water phase oxidation method is adopted to synthesize polydopamine nano-particles with uniform size, and the surfaces of the polydopamine nano-particles are modified with a layer of polyethylene glycol (PEG) and loaded with IX through a Michael addition reaction and a condensation reaction respectively. Nuclides 131I, 99mTc and 177Lu are labeled on PDA through a chloramine-T method, a stannous chloride (SnCl2) reduction method and a DOTA chelation method respectively, the labeling yield and stability are detected, and the obtained nuclide-loaded probe is applied to breast cancer diagnosis and combined treatment. Research results show that the PDA nanoparticles have a good photo-thermal effect, and controllable photo-thermal therapy is achieved by adjusting laser power and probe concentration.

A method for producing a radioactive metal complex includes a step of allowing a radioactive metal to react with DOTA or a derivative thereof as a ligand in a reaction liquid to form a radioactive metal complex. The reaction liquid contains water, a buffer, and a water-soluble organic solvent. The radioactive metal is ⁸⁹Zr or ²²⁵Ac. The ligand may have, in the structure thereof, a group to which a peptide is linked. The content of the water-soluble organic solvent in the reaction liquid is preferably 2% by volume or more and 50% by volume or less. The radioactive metal is preferably allowed to react with the ligand in the reaction liquid at 30° C. or higher and 80° C. or lower.