WO2009018761A1 - Agent de développement à base d'apatite et utilisation de l'agent de développement en tomographie par émission de positrons - Google Patents

Agent de développement à base d'apatite et utilisation de l'agent de développement en tomographie par émission de positrons Download PDF

Info

Publication number
WO2009018761A1
WO2009018761A1 PCT/CN2008/071841 CN2008071841W WO2009018761A1 WO 2009018761 A1 WO2009018761 A1 WO 2009018761A1 CN 2008071841 W CN2008071841 W CN 2008071841W WO 2009018761 A1 WO2009018761 A1 WO 2009018761A1
Authority
WO
WIPO (PCT)
Prior art keywords
apatite
developer
aqueous solution
calcium
positron
Prior art date
Application number
PCT/CN2008/071841
Other languages
English (en)
Chinese (zh)
Inventor
Shengmin Zhang
Wei Zhou
Original Assignee
Huazhong University Of Science And Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Huazhong University Of Science And Technology filed Critical Huazhong University Of Science And Technology
Publication of WO2009018761A1 publication Critical patent/WO2009018761A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
    • A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus

Definitions

  • the present invention relates to the field of biomedical materials, medical imaging, specific preparation methods of apatite developers and positron emission tomography (PET) imaging. Background technique
  • Apatite developer labeled with a positron nuclides is a developer dedicated to apatite positron emission tomography (PET) imaging.
  • PET positron emission tomography
  • the development of imaging agents themselves is currently the most popular and cutting-edge research topic in the field of molecular nuclear medicine and molecular imaging, because the prerequisite for PET imaging is the preparation of various specific PET drugs (also known as A positron imaging agent or a positron drug).
  • a positron imaging agent or a positron drug also known as A positron imaging agent or a positron drug
  • Apatite is the main inorganic component of human and animal bone tissue, including hydroxyapatite, fluorine-substituted apatite and a series of modified apatites doped with magnesium, silver, zinc and carbonate.
  • the material has excellent biocompatibility and biological activity. Since the advent of the 1970s, apatite has been widely used as a biomedical filler, coating material, etc. in the clinic. In recent years, studies have found that apatite also has an inhibitory effect on more than 10 kinds of cancer cells, but has little effect on normal cells, and has no effect at all, thus showing a certain degree of targeting and broad-spectrum anticancer effects. Many unique physical and chemical properties make in-vivo evaluation work closely related to apatite medical treatment become one of the important research topics in the field of biomaterials at home and abroad.
  • the markers related to common apatite at home and abroad mainly include 45 Ca, 99m Tc-bisphosphonate complexes and ruthenium markers. These methods can only reflect the distribution and metabolism of local regions of interest, most In this case, the model animal needs to be sacrificed in order to obtain the desired result. The technical operation is difficult, and it is difficult to obtain a complete three-dimensional dynamic distribution and metabolic image. It has not been applied to the real-time imaging of apatite and the apatite drug generation. Report on dynamics.
  • apatite developer This type of apatite developer, first reported in this patent, is a positron-emitting nucleus added during the synthesis of apatite.
  • the positron nuclides are contained in the apatite crystal structure by replacing part of the OH- in the apatite.
  • positron-labeled apatite developer In the positron-labeled apatite developer.
  • the nuclide emits a positron during the decay process.
  • This positron travels a short distance (linm) in the body tissue, annihilating radiation with electrons in the surrounding material, producing two Y-photons of opposite energy and equal energy.
  • PET imaging detects these annihilation radiation photons and obtains a fault map of positron nuclides in the body, revealing the spatial distribution, density, and specific receptor target tissues or cells of the positron-labeled developer in the body. Combined affinity.
  • Replacement page ( ⁇ Article 26) Since positron-emitting nuclei are chemically identical to ordinary ions, they are chemically identical to ordinary ions.
  • the apatite developer is consistent with the properties of the parent apatite, and the related metabolic kinetics of the apatite can be directly studied after PET imaging.
  • the three-dimensional dynamic distribution image of the apatite in the whole body of the animal can be obtained in real time by PET imaging, and dynamic PET imaging is performed.
  • the blood concentration of the blood and various organs at different times can be measured, and the pharmacokinetic parameters and drug metabolism rate of the apatite can be calculated.
  • the quantitative analysis is sensitive, accurate and accurate, and the animal model can be reused. Summary of the invention
  • the object of the present invention is to develop a class of apatite developer, which directly observes the in-situ distribution of apatite by PET imaging technology, and satisfies various in-vivo evaluation work closely related to apatite medical treatment.
  • An apatite developer characterized in that: the developer contains a crystal structure of a nicotinic nuclides, which is obtained by replacing a part of OH in the apatite by adding a positron nuclides during the apatite synthesis process. , its molecular formula is
  • ⁇ is Mg, Sr, La, Y, Ce or ⁇ , 0 ⁇ 10;
  • Q is C0 3 2 , 0 ⁇ ⁇ ⁇ 6;
  • R is C0 3 2 -, F- or Cl-, 0 ⁇ ⁇ ⁇ 2;
  • A is 18 F, 76 Br, 75 Br or 124 I.
  • the preparation steps include:
  • the concentration of the aqueous solution is 0. 006 ⁇ 0. 6mol / / _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
  • a dropping step the aqueous solution of the phosphorus salt prepared in the step (1) is added dropwise to the aqueous solution of the calcium salt, and the aqueous solution of the calcium salt is added to the aqueous solution at any time to maintain the pH of the mixed solution 7. 0 to: 12;
  • positron nuclides are 18 F, 76 Br, "Br or 124 1 produced by a cyclotron or generator;
  • the calcium salt aqueous solution is prepared by using any one of calcium nitrate tetrahydrate, calcium acetate monohydrate, calcium chloride, calcium hydroxide and calcium carbonate;
  • the aqueous solution is prepared using any one of phosphoric acid, diammonium hydrogen phosphate, and ammonium dihydrogen phosphate.
  • modified cationic magnesium, strontium, zinc, cerium, lanthanum, boron and cerium Adding one or more of modified cationic magnesium, strontium, zinc, cerium, lanthanum, boron and cerium to the aqueous solution of the calcium salt, wherein the modified cation accounts for the molar ratio of calcium in the apatite developer a%, where 0 a ⁇ 100.
  • modified anion fluorine, chlorine and carbonate Adding one or more of the modified anion fluorine, chlorine and carbonate to the aqueous solution of the phosphorus salt, wherein the modified anion accounts for the molar ratio of the hydroxide group and the phosphate group in the apatite developer, respectively. b% and c%, where 0 b ⁇ 100, 0 c ⁇ 100, and b + c ⁇ 0, b + c ⁇ 200.
  • the method for producing an apatite developer is further characterized in that the entire process can be automated and continuous in a closed protective system, and the radiochemical purity of the final product apatite developer can be controlled.
  • apatite developer is characterized in that it can be used for real-time imaging of positron emission tomography, providing new theoretical and methodological guidance for biomedical evaluation of apatite.
  • apatite developer characterized in that it is used for preparing a pharmaceutical preparation comprising an apatite developer and a pharmaceutically acceptable excipient, the pharmaceutical preparation comprising the apatite developer of the invention;
  • the formulation is suitable for administration as an imaging enhancer, and the apatite developer is present in an amount sufficient to achieve or enhance positron emission tomography.
  • PET imaging technology allows apatite to enter substantive research as a drug or drug carrier.
  • the present invention describes for the first time a method for preparing an apatite developer and PET imaging thereof.
  • Animal experiments have shown that an injection solution containing an apatite developer is introduced into the body from an experimental rabbit ear vein, not only by positron emission tomography
  • the imaging method was used to simulate the whole body of the rabbit in real time, and the dynamics of the blood and the radiation concentration of each organ at different times were measured by dynamic PET imaging, and the pharmacokinetic parameters and drug metabolism rate of the apatite were calculated.
  • Example 1 The invention is further illustrated by the following specific examples. Example 1
  • the generated positron nuclides 18 F were injected into the mixed solution, and the stirring state was maintained, and the temperature was maintained at 60 °. After the lapse of 3 hours, the suspension containing the apatite developer was taken out and washed with deionized water for 3 times, and the specific activity was 0.134 mCi/mg.
  • the positron nuclides 18 F produced by the cyclotron were injected into the mixture, and the stirring was continued while maintaining the temperature at 60 ° C. After the lapse of 3 hours, the suspension containing the apatite developer was taken out and washed with deionized water for 5 times, and the specific activity was 0.078 mCi/mg.
  • the suspension containing the apatite developer was taken out, washed 3 times with deionized water, and the suspension containing the apatite developer was washed 3 times with deionized water.
  • the specific activity was 0. 251 mCi/mg.
  • the positron nuclides 18 F produced by the cyclotron were injected into the mixture and maintained under stirring at a constant temperature of 60 °C. After 3 hours, the suspension containing the apatite developer was taken out and washed 3 times with deionized water to measure the specific activity.
  • the C0 2 was passed through, and then the aqueous solution of diammonium hydrogen phosphate was slowly added dropwise to the aqueous solution of calcium nitrate tetrahydrate by a constant flow pump to maintain the oil bath for 70 Torr.
  • the positron nuclides 18 F produced by the cyclotron were injected into the mixture, and the stirring was continued while maintaining the temperature at 60 °C. After that, the suspension containing the apatite developer was taken out and washed with deionized water for 3 times, and the specific activity was 0.14 mCi/ m g.
  • the radionuclide 18 F was injected into the mixture and maintained under stirring at a constant temperature of 60 Torr. After that, the suspension containing the apatite developer was taken out and washed with deionized water for 4 times, and the specific activity was 0.140 mCi/mg.
  • the bath was heated at 60 ° C, and the positron nuclides 18 F produced by the cyclotron were injected into the mixture, and the stirring was maintained at a constant temperature of 60 Torr. 164mCi/mgo ⁇ After the lapse of the activity of 0. 164mCi / mgo

Landscapes

  • Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Nuclear Medicine (AREA)

Abstract

L'invention se rapporte à un procédé de production d'un agent de développement à base d'apatite comprenant l'étape qui consiste à ajouter le nucléide émetteur de positron au moment où l'apatite est synthétisée. Un agent de développement à base d'apatite est proposé et peut être utilisé en tomographie par émission de positrons. L'expérimentation animale montre que, lorsque l'agent de développement à base d'apatite est injecté dans le lapin par la veine du bord de l'oreille, il peut donner une image en temps réel de l'ensemble du lapin à l'aide de la tomographie par émission de positrons, et il permet également de mesurer la viscosité du sang et l'épaisseur d'émission de chaque organe à l'aide de la tomographie dynamique par émission de positrons. En outre, le paramètre dynamique du métabolisme médicamenteux de l'apatite et la vitesse du métabolisme médicamenteux peuvent également être calculés. L'invention propose simultanément la formulation pharmaceutique comprenant l'agent de développement à base d'apatite et l'excipient pharmaceutique acceptable.
PCT/CN2008/071841 2007-08-03 2008-07-31 Agent de développement à base d'apatite et utilisation de l'agent de développement en tomographie par émission de positrons WO2009018761A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN2007100528934A CN101125208B (zh) 2007-08-03 2007-08-03 一种磷灰石显影剂的制备方法
CN200710052893.4 2007-08-03

Publications (1)

Publication Number Publication Date
WO2009018761A1 true WO2009018761A1 (fr) 2009-02-12

Family

ID=39093399

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2008/071841 WO2009018761A1 (fr) 2007-08-03 2008-07-31 Agent de développement à base d'apatite et utilisation de l'agent de développement en tomographie par émission de positrons

Country Status (2)

Country Link
CN (1) CN101125208B (fr)
WO (1) WO2009018761A1 (fr)

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101125208B (zh) * 2007-08-03 2011-08-31 华中科技大学 一种磷灰石显影剂的制备方法
CN114569216B (zh) * 2022-05-07 2023-01-03 中南大学湘雅医院 减胎穿刺针组件

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4243652A (en) * 1978-07-14 1981-01-06 The Procter & Gamble Company Gastrointestinal scanning agent
JPH0658932A (ja) * 1992-08-12 1994-03-04 Yamasa Shoyu Co Ltd 活性なオステオカルシンの測定法
WO2005079867A2 (fr) * 2004-02-20 2005-09-01 Algeta As Particules d'hydroxyapatite emettrices de rayons alpha
CN101125208A (zh) * 2007-08-03 2008-02-20 华中科技大学 一种磷灰石显影剂及其正电子发射断层成像

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4243652A (en) * 1978-07-14 1981-01-06 The Procter & Gamble Company Gastrointestinal scanning agent
JPH0658932A (ja) * 1992-08-12 1994-03-04 Yamasa Shoyu Co Ltd 活性なオステオカルシンの測定法
WO2005079867A2 (fr) * 2004-02-20 2005-09-01 Algeta As Particules d'hydroxyapatite emettrices de rayons alpha
CN101125208A (zh) * 2007-08-03 2008-02-20 华中科技大学 一种磷灰石显影剂及其正电子发射断层成像

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
JOYSTON-BECHAL S. ET AL.: "The role of iso-ionic exchange in the uptake of 18F labelled fluoride by hydroxyapatite and enamel", ARCHS. ORAL BIOL., vol. 12, no. 10, 1967, pages 1097 - 1105 *
MITTERHAUSER M. ET AL.: "Binding studies of [18F]-fluoride and polyphosphonates radiolabeled with [111In],[9mTc],[153Sm], and [188Re] on bone compartments: a new model for the pre vivo evaluation of bone seekers?", BONE, vol. 34, no. 5, 2004, pages 835 - 844 *

Also Published As

Publication number Publication date
CN101125208A (zh) 2008-02-20
CN101125208B (zh) 2011-08-31

Similar Documents

Publication Publication Date Title
Chakraborty et al. Comparative studies of 177Lu–EDTMP and 177Lu–DOTMP as potential agents for palliative radiotherapy of bone metastasis
Shoup et al. Evaluation of (4-[18 F] Fluorophenyl) triphenylphosphonium ion. A potential myocardial blood flow agent for PET
Meckel et al. In vivo comparison of DOTA based 68Ga-labelled bisphosphonates for bone imaging in non-tumour models
CN102458396B (zh) 使用抗坏血酸稳定化放射性药物组合物
Louw et al. Evaluation of samarium-153 and holmium-166-EDTMP in the normal baboon model
Zakaly et al. Comparative studies on the potential use of 177Lu-based radiopharmaceuticals for the palliative therapy of bone metastases
JPS5896031A (ja) 放射性診断剤およびその製造用組成物
Das et al. Formulation, preclinical evaluation, and preliminary clinical investigation of an in-house freeze-dried EDTMP kit suitable for the preparation of 177Lu-EDTMP
Vats et al. Radiolabeling, stability studies, and pharmacokinetic evaluation of thulium-170-labeled acyclic and cyclic polyaminopolyphosphonic acids
CN1950329B (zh) 放射性酪氨酸衍生物、其制造方法、其使用、正电子成像用标识剂和肿瘤的恶性度评价药剂
Yousefnia et al. Estimated human absorbed dose of 177Lu–BPAMD based on mice data: Comparison with 177Lu–EDTMP
Choi et al. Theranostics through utilizing cherenkov radiation of radioisotope Zr-89 with a nanocomposite combination of TiO2 and MnO2
Mirković et al. Investigation of 177Lu-labeled HEDP, DPD, and IDP as potential bone pain palliation agents
Vimalnath et al. Practicality of production of 32P by direct neutron activation for its utilization in bone pain palliation as Na3 [32P] PO4
BAHRAMI et al. Production, quality control and biological evaluation of 153Sm-EDTMP in wild-type rodents
WO2009018761A1 (fr) Agent de développement à base d'apatite et utilisation de l'agent de développement en tomographie par émission de positrons
RU2568888C1 (ru) СПОСОБ И СОСТАВ ДЛЯ ПОЛУЧЕНИЯ РЕАГЕНТА ДЛЯ РАДИОНУКЛИДНОЙ ДИАГНОСТИКИ НА ОСНОВЕ МЕЧЕННОЙ ТЕХНЕЦИЕМ-99m 5-ТИО-D-ГЛЮКОЗЫ
US20220313844A1 (en) Radioactive yttrium phosphate suspension and method of preparing the same
Jalilian et al. Preclinical studies of [Cu] ATSM as a PET radiopharmaceutical for fibrosarcoma imaging
JP5956533B2 (ja) 放射ターゲット薬物調製用キット及び放射ターゲット薬物の調製方法及び用途
Zhou et al. Preliminary Studies of 177Lu-Diethylenetriamine Penta-Acetic Acid-Deoxyglucose in Hepatic Tumor-Bearing Mice
Kilian et al. Imaging of hypoxia in small animals with F fluoromisonidasole
Dence et al. Radiochemical synthesis, rodent biodistribution and tumor uptake, and dosimetry calculations of [11 C] methylated LY2181308
CN116251201B (zh) 抗类风湿性关节炎的自组装水凝胶及其制备方法与应用
CN102020768B (zh) 一种99mTc配合物、其制备方法、中间体及其应用

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08783834

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08783834

Country of ref document: EP

Kind code of ref document: A1