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JP-7855604-B2 - Method for producing high-purity, high-specific-activity radionuclides

JP7855604B2JP 7855604 B2JP7855604 B2JP 7855604B2JP-7855604-B2

Inventors

  • フォルメント カヴァリエ，ロベルト
  • ザヒ，リエス
  • ハダッド，フェリド
  • ストラ，ティエリ

Assignees

  • アドバンスド アクセラレーター アプリケーションズ
  • アロナックス
  • オーガナイゼーション ヨーロペニー ポア ラ ルシェルシュ ニュクレール

Dates

Publication Date
20260508
Application Date
20211209
Priority Date
20201210

Claims (7)

  1. a) A step of irradiating a target with a particle beam to obtain an irradiation target containing the target radionuclide, b) A step of chemically extracting the target radionuclide from the irradiation target, c) A method for producing a high specific activity radionuclide, comprising the step of mass-separating a batch of target radionuclides to obtain a high specific activity radionuclide , If the high specific activity radionuclide is selected from scandium isotopes, the target of the choice includes metallic titanium, and step b) includes the steps of exposing metallic titanium to an HBr solution while applying a voltage, dissolving the solution in an acid, and passing the resulting solution through a resin. A method for producing a high specific activity radionuclide, wherein the target of the choice is selected from isotopes of terbium, and step b) comprises dissolving metallic gadolinium in a nitric acid solution and passing the resulting solution through a resin .
  2. The method for producing a high specific activity radionuclide according to claim 1, wherein the particle beam in step a) is a proton beam exhibiting an energy between 18 and 200 MeV.
  3. A method for producing a high specific activity radionuclide according to claim 1, wherein step b) includes liquid-liquid extraction.
  4. A method for producing a high specific activity radionuclide according to claim 1, wherein step b) includes liquid-solid extraction.
  5. Step b) A step of pouring the liquid solution obtained in step b) onto the support, A step of heating and concentrating the liquid solution on the support, and depositing the radioactive nuclide on the support, A method for producing a high specific activity radionuclide according to claim 1, further comprising a target coupling step b2) which includes inserting the support containing the radionuclide of the objective into a mass separator.
  6. The method for producing a high specific activity radionuclide according to claim 5 , wherein the support in step b2) is a metal support.
  7. A method for producing a high specific activity radionuclide according to claim 1, further comprising a second chemical separation and purification step d2) after the mass separation step.

Description

This invention relates to the field of producing high-purity, high-specific-activity radionuclides, for example, medical use on an industrial scale. Radioactive isotopes, or radionuclides, are widely used in the fields of life sciences, research, and medicine, such as nuclear medicine. In nuclear medicine, they are used particularly for imaging and radiotherapy for cancer. To reach the target, radioisotopes can be attached to molecules/mediums and injected in solution (e.g., citrate) or independently (Zimmermann, Nuclear Medicine: Radioactivity for Diagnosis and Therapy - 2017 - EDP Science Edition). Radionuclides can be bound to a medium using chelating agents and linkers. Chelating agents are substances that can form several bonds to a single atom or ion, and are also defined as polydentate ligands. When using a medium, it is necessary to find appropriate biological targets that adhere to tumor cells without harming normal cells. This is possible by using peptides or antibodies that are preferentially taken up by specific receptors, and by selecting those target receptors that are more frequently present in tumor cells than in normal cells. Radioisotopes labeled on the same medium, preferably peptides or antibodies, that ensure imaging and therapy are defined as theranostic (or theragnostic) radioisotopes (Langbein et al: J Nucl Med. 2019 Sep;60(Suppl 2):13S-19S). One such important application of radioisotopes is the diagnosis and treatment of diseases, such as cancer. For example, there has been considerable progress in the use of radiolabeled tumor-selective peptides and monoclonal antibodies in the diagnosis and treatment of several types of cancer over the past two decades. The concept of localizing cytotoxic radionuclides to cancer cells is an important complement to conventional forms of radiotherapy. Theoretically, the interaction of radiopharmaceuticals with target cells can concentrate the absorbed radiation dose on the cancer cell site, minimizing damage to normal surrounding cells and tissues (Zhejiang et al. Univ Sci B. 2014 Oct; 15(10): 845-863; Zukotynski et al. Biomark Cancer. 2016; 8(Suppl 2): 35-38). The selection of radioisotopes is based on the nature of the emitted radiation, its physical properties (e.g., energy, half-life, and decay series), as well as its chemical properties. Based on the radiation they emit, radioactive isotopes can be further divided into gamma (γ) ray emitters, beta (positron β+ or electron β-) particle emitters, and alpha (α) particle emitters, Auger emitters, or combinations thereof. Further advances in the field of nuclear medicine will require investigations into the use of new isotopes, new sources, and isotope production methods. Three main direct or indirect nuclear processes that lead to the production of intended radioactive isotopes can be defined and identified as methods for producing radionuclides: nuclear reactions carried out using particle accelerators, such as cyclotrons, linear accelerators, and electron accelerators; nuclear reactions carried out in nuclear reactors; and the production of optimal radioactive isotopes obtained by chemical elution processes inside so-called generators. Furthermore, the above production methods can be combined with other techniques to improve the quality of the products. Radioactive isotopes can be produced by transmuting radionuclides by colliding charged particles (mainly protons, deuterons, or alpha particles) with a target nucleus. These charged particles need to be accelerated to at least a few MeV energies to overcome the Coulomb barrier of the target nucleus and enable nuclear reactions. As a result, particle accelerators are required. Due to their practical properties and high current performance across the entire desired energy range (10–100 MeV), cyclotrons have almost without exception been chosen as the most convenient option for radioactive isotope production since the 1950s, with the exception of a few therapeutic radionuclides that can be produced more conveniently in nuclear reactors. However, only a few radioactive isotopes can be produced in cyclotrons with high radionuclide purity and high production yield. To improve the availability of several other radionuclides, for example, U.S. Patent Application Publication No. 20170169908 describes the use of a 70 MeV cyclotron with an online mass separation system, which means simultaneous or pseudo-simultaneous irradiation of a target by the cyclotron and separation thereof by online mass separation for the production of radionuclides. However, these methods impose constraints on the target to be irradiated, which must have determined properties, and this can potentially reduce the overall yield (e.g., porosity, evaporation temperature, etc.) and limit the radioisotopes that can be produced with high efficiency. Another example is U.S. Patent No. 9202600 (US9202600B2) (Canadian Patent No. 2594829 (CA2594829C) and British Patent No. 2436508 (GB2436508B