Method for purification of 225AC from irradiated 226RA-targets

{
  "publication_number": "US9790573B2",
  "country": "US",
  "kind": "B2",
  "title": "Method for purification of 225AC from irradiated 226RA-targets",
  "abstract": "The present invention describes a method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support comprising a leaching treatment of the 225 Ra-targets for leaching essentially for the entirety of 223 Ac and 226 Ra with nitric or hydrochloric acid, followed by a first extraction chromatography for separating 225 Ac from 226 Ra and other Ra-isotops and a second extraction chromotography for separating 225 Ac from 210 Po and 210 Pb. The finally purified 225 Ac can be used to prepare compositions useful for pharmaceutical purposes.",
  "claims": [
    "1. A method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support, comprising the following steps: a) leaching 225 Ac and 226 Ra from one or more 226 Ra-targets with a nitric acid solvent in a refluxing/distillation arrangement to generate one or more 225 Ac and 226 Ra containing extracts, wherein said nitric acid solvent has a concentration range of about 0.001 M to about 2 M; b) concentrating the 225 Ac and 226 Ra containing extracts, wherein the concentrating results in a 225 Ac and 226 Ra containing extract having a concentration of about 1.5 M to about 10 M of HNO 3; c) separating 225 Ac from 226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IA, wherein in formula IA: R1a, R2a, R3a, R4a independently is octyl or 2-ethylhexyl; d) allowing the 226 Ra to flow through and then eluting 225 Ac retained on the solid support with nitric acid having a concentration between about 0.01M and about 0.3M or with hydrochloric acid having a concentration between about 0.05M and about 1M; e) separating 225 Ac from 210 Po and 210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV, wherein in formula III: R8 and R9 independently is H, C 1 -C 6 alkyl, or t-butyl; and wherein in formula IV: R10 is C 4 to C 12 alkyl; f) using 2M HCl as mobile phase; and g) recovering 225 Ac as a flow-through separately from 210 Po and 210 Pb, which are retained on the solid support.",
    "2. A method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support, comprising the following steps: a) leaching 225 Ac and 226 Ra from one or more 226 Ra-targets with a nitric acid solvent in a refluxing/distillation arrangement to generate one or more 225 Ac and 226 Ra containing extracts, wherein said nitric acid solvent has a concentration range of about 0.001 M to about 2 M; b) concentrating the 225 Ac and 226 Ra containing extracts, wherein the concentrating results in a 225 Ac and 226 Ra containing extract having a concentration of about 1.5 M to about 10 M of HNO 3; c) separating 225 Ac from 226 Ra and other Ra isotopes by means of at least one first extraction chromatography with a solid support material having a first extractant system coated thereon, comprising at least one compound in accordance with general formula IB, d) allowing the 226 Ra to flow through and then eluting 225 Ac retained on the solid support with nitric acid having a concentration between about 0.02 M and about 0.1 M; e) separating 225 Ac from 210 Po and 210 Pb by means of at least one second extraction chromatography with a solid support material having a second extractant system coated thereon, comprising at least one compound in accordance with general formula III in at least one compound in accordance with general formula IV, wherein in formula III: R8 and R9 independently is H, C 1 -C 6 alkyl, or t-butyl; and wherein in formula IV: R10 is C 4 to C 12 alkyl; f) using 2M HCl as mobile phase; and g) recovering 225 Ac as a flow-through separately from 210 Po and 210 Pb which are retained on the solid support.",
    "3. The method of any one of claims 1 to 2, wherein the support is a metal, and is selected from the group consisting of Aluminum or Aluminum alloys, passivated Aluminum, anodized Aluminum, coated Aluminum, Aluminum coated with an element of a Platinum group, precious metals, elements from a Platinum group; and mixtures thereof.",
    "4. The method of any one of claims 1 to 2, wherein the second extractant system is a crown ether in accordance with formula V: in 1-octanol.",
    "5. The method of any one of claims 1 to 2, wherein the second extractant system is 4,4′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol.",
    "6. The method of any one of claims 1 to 2, wherein the second extractant system is 4,5′-bis(t-butylcyclohexano)-18-crown-6 in 1-octanol.",
    "7. The method of any one of claims 1 to 2, wherein the first extraction chromatography of step c) is repeated one or more times.",
    "8. The method of any one of claims 1 to 2, wherein the second extraction chromatography of step e) is repeated one or more times.",
    "9. The method of any one of claims 1 to 2, further comprising removing Rn from the support or the 225 Ac and 226 Ra containing extract during step a).",
    "10. The method of claim 9, wherein the Rn is removed by means of a first alkaline trap to neutralize acidic vapours, a subsequent silica trap to absorb water, and a final activated coal trap.",
    "11. The method of any one of claims 1 to 2, further comprising a step of recovering a 226 Ra flow-through of step d).",
    "12. The method of any one of claims 1 to 2, further comprising a step of eluting 210 Po from the solid support of the second extraction chromatography in step g) by means of concentrated nitric acid or concentrated hydrochloric acid.",
    "13. The method of any one of claims 1 to 2, wherein a fraction of a purification step is examined by means of α- and/or γ-spectroscopy.",
    "14. The method of any one of claims 1 to 2, wherein a fraction of a purification step containing any one of: a) 225 Ac; b) Ra-isotopes; c) 210 Po; and d) 210 Pb is subjected to an evaporation step.",
    "15. The method of any one of claims 1 to 2, further comprising a step of removing one or more organic impurities from a fraction of a purification step.",
    "16. The method of any one of claims 1 to 2, wherein the nitric acid solvent of step a) has a concentration of about 0.1M.",
    "17. The method of any one of claims 1 to 2, wherein the nitric acid solvent of step a) is used at a temperature of about 30 to 90° C.",
    "18. The method of claim 10, wherein the activated coal trap is cooled.",
    "19. The method of any one of claims 1 to 2, further comprising a step of eluting 210 Pb from the solid support of the second extraction chromatography in step g) by means of concentrated hydrochloric acid or EDTA.",
    "20. The method of claim 14, wherein the fraction is evaporated to a wet or a dry residue.",
    "21. The method of claim 14, wherein the fraction is redissolved.",
    "22. The method of claim 15, wherein the step of removing one or more organic impurities from a fraction of a purification step is performed by passing the fraction through a resin comprising a non-ionic acrylic ester polymer."
  ],
  "description_excerpt": "This application is a Continuation of U.S. patent application Ser. No. 14/231,354 filed Mar. 31, 2014, which is a Continuation of U.S. patent application Ser. No. 13/893,056 filed May 13, 2013, which is a Continuation of U.S. patent application Ser. No. 12/280,079 filed Feb. 6, 2009, which is a U.S. National Phase Application under 35 U.S.C. §371 of International Patent Application No. PCT/EP2007/001424, filed Feb. 19, 2007, which claims priority to German Patent Application No. 102006008023.8, filed Feb. 21, 2006, each of which is herein incorporated by reference in its entirety.\n\nThe present invention relates to a Method for purification of 225 Ac from irradiated 226 Ra-targets provided on a support according to claims 1 to 3. Furthermore, the invention relates to an 225 Ac-containing radionuclide composition in accordance with claim 21.\n\nIn particular, the radionuclide 225 Ac can be successfully used in nuclear medicine - bound to tumorspecific antibodies - in various clinical trials in the treatment of cancer, particularly in form of its daughter nuclide 213 Bi.\n\nAlready in 1993, criteria for the selection of radionuclides for immunotherapy with α-emitters and β-emitters were provided for the first time (GEERLINGS, M. W. (1993): Int. J. Biol. Markers, 8, 180-186: “Radionuclides for radioiminunotherapy: criteria for selection”) where it turned out due to the difference in energy that the radioactivity of α-emitters to be applied may be more than 1000 times lower than that of β-emitters, if a comparable effect is to be achieved.",
  "cpc": [
    "C22B 60/0295",
    "A61K 51/00",
    "A61P 35/00",
    "A61P 35/02",
    "B01D 15/206",
    "B01D 15/26",
    "C22B 7/005",
    "C22B 7/007",
    "C22B 7/009",
    "G21G 1/001",
    "G21G 2001/0089",
    "G21G 4/08",
    "Y02P 10/20"
  ],
  "ipc": [
    "B01D 15/20",
    "C22B 60/02",
    "C22B 7/00",
    "G21G 1/00",
    "A61K 51/00",
    "A61M 36/14"
  ],
  "assignees": [
    "Actinium Pharmaceuticals Inc"
  ],
  "inventors": [
    "Josue Manuel Moreno Bermudez",
    "Andreas Turler",
    "Richard Henkelmann",
    "Eva Kabai",
    "Ernst Huenges"
  ],
  "filing_date": "2016-11-22",
  "publication_date": "2017-10-17",
  "grant_date": "2017-10-17",
  "priority_date": "2006-02-21",
  "application_number": "US-201615359053-A",
  "family_id": "38319730",
  "cited_by_count": 12,
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