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WO1993023854A1 - Procede destine a separer l'yttrium-90 du strontium-90 - Google Patents

Procede destine a separer l'yttrium-90 du strontium-90 Download PDF

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Publication number
WO1993023854A1
WO1993023854A1 PCT/US1993/004282 US9304282W WO9323854A1 WO 1993023854 A1 WO1993023854 A1 WO 1993023854A1 US 9304282 W US9304282 W US 9304282W WO 9323854 A1 WO9323854 A1 WO 9323854A1
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WO
WIPO (PCT)
Prior art keywords
source
cow
organic extractant
nitric acid
purifying
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US1993/004282
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English (en)
Inventor
Lane A. Bray
David W. Wester
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Battelle Memorial Institute Inc
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Battelle Memorial Institute Inc
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 Battelle Memorial Institute Inc filed Critical Battelle Memorial Institute Inc
Publication of WO1993023854A1 publication Critical patent/WO1993023854A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • G—PHYSICS
    • G21—NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21G—CONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G4/00—Radioactive sources
    • G21G4/04—Radioactive sources other than neutron sources
    • G21G4/06—Radioactive sources other than neutron sources characterised by constructional features
    • G21G4/08—Radioactive sources other than neutron sources characterised by constructional features specially adapted for medical application
    • 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
    • A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
    • A61K51/1282—Devices used in vivo and carrying the radioactive therapeutic or diagnostic agent, therapeutic or in vivo diagnostic kits, stents

Definitions

  • Yttrium-90 with a half-life of 64 hours is finding increasing use in the treatment of various forms of cancer.
  • the National Cancer Institute has listed Y-90 as one of the top three radioactive isotopes being evaluated for use in cancer therapy. Medical researchers studying cancer treatment for the past five years have developed techniques using radioactive Y-90 labeled monoclonal antibodies to treat fatal adult T-cell leukemia. Others are using Y-90 labeled antibodies for studies of tumor therapy of ovarian, colon, and lymphatic cancers.
  • FIG. 1 is a graph of chemical equilibrium constants for Y-90 and Sr-90 in nitric acid and di(2-ethylhexyl)- phosphoric acid (HDEHP) diluted with N-dodecane.
  • the present invention is a method for purifying Y-90, by separating Y-90 from a source mixture of Sr-90 and Y-90 primarily by solvent extraction of the Y-90 into a dilute organic solution of highly purified di(2-ethylhexyl) phosphoric acid (HDEHP) in a diluent of N-dodecane.
  • HDEHP highly purified di(2-ethylhexyl) phosphoric acid
  • Yttrium-90 can be effectively extracted into an organic phase in dilute nitric acid ("0.3M). As shown in FIG.
  • a single-stage separation of Y-90 from Sr-90 based on an equilibrium constant for Y-90 of 10 and an equilibrium constant for Sr-90 of 0.001 achieves a Sr-90/Y-90 separation ratio in the organic phase of l(10E-4).
  • Further Sr-90 removal to achieve separation ratios at or below l(10E-8) is accomplished by washing the Y-90 organic phase with dilute nitric acid ( " 0.3M HN0 3 ).
  • Achieving separation ratios at or below l(10E-8) is done in the present invention by applying two criteria.
  • the first criteria is limiting the amount of impurities introduced into the processing by selecting highly purified reagents and by purifying the reactants prior to use.
  • the second criteria is carefully selecting the type and order of processing steps.
  • the processing steps include:
  • Raw Sr-90/Y-90 source containing Cs-137 in addition to the first group of impurities is obtained as a by-product of nuclear waste reprocessing. Separation of the impurities is accomplished by first removing any and all ionic impurities except the Cs-137, then secondly removing the Cs-137.
  • the first group of ionic impurities are removed by adding sodium hydroxide to raw Sr-90/Y-90 source. Sufficient sodium hydroxide is added to obtain a pH between about 10 to about 12. It is preferred that the sodium hydroxide contain no or undetectable amounts of carbonate.
  • the first group of ionic impurities precipitates with the sodium hydroxide forming hydroxide solids.
  • the "cow” is set aside to allow time for ingrowth, i.e., decay of a portion of Sr-90 (half-life of 30 years) to Y-90 (half-life of 60 hours) .
  • the amount of time is preferably from about l week to about 2 weeks providing ingrowth of maximum Y-90 radioactivity from about 80% to about 95%.
  • the organic extractant used to separate Sr-90 from Y-90 is obtained as reagent grade HDEHP, available from chemical suppliers; for example, Eastman, Catalog Number 8755 [CH 3 (CH 2 ) 3 CH(C 2 H 5 )CH 2 0]POOH, then further purified from iron and other metals.
  • Rea ⁇ gent grade HDEHP contains traces of metallic impurities including iron. Washing the HDEHP with hydrochloric acid or nitric acid removes most metallic impurities, but does not completely remove iron which is tightly held. Iron remaining in the HDEHP will slowly leach out of the HDEHP into a product solution during extraction, thereby leav- ing an iron impurity in the product solution. Therefore, the HDEHP used in the present invention is first purified by a method described by Partridge and Jensen (1965) .
  • the first or second precipitate is converted back to HDEHP by washing the precipitate with a dilute aqueous acid.
  • Partridge and Jensen suggest hydrochloric acid.
  • the acid wash may be repeated until all Cu(II) is removed.
  • the remaining aqueous acid is removed with water washes.
  • the remaining water is removed with a rotating evaporator.
  • the resulting concentration of purified HDEHP is about 3M.
  • the dried Sr-90/Y-90 source "cow” is adjusted to a volume equiv ⁇ alent to a volume of purified organic extractant by dissolving in nitric acid.
  • An amount of nitric acid of from about 3 L to about 10 L, but preferably about 5 L, is added to the "cow”.
  • Both the volume adjusted "cow” and the volume adjusted purified organic extractant are further concentration adjusted based upon FIG. 1 from about 0.25M to about 0.35M, but preferably about 0.3M, thereby producing a separation ready source.
  • the methods of purification and pretreatment of a raw Sr-90 source are appropriate for producing any amount of fresh Sr-90 source "cow” but it is preferable to produce from about 4 mL to about 10 mL of separation ready source.
  • the purified HDEHP organic extractant diluted to 0.3M with N-Dodecane, is acid washed to equilibrate the organic with acid and to produce about 10 mL of separa ⁇ tion ready extractant.
  • the purified HDEHP organic extractant is first washed twice with concentrated nitric acid of preferred concentrations ranging from about 7M to 10M, but most preferably about 7M.
  • the concentrated acid washes are followed by two scrubs using dilute nitric acid. It is preferred that the dilute nitric acid have concentrations ranging from about 0.1M to about 0.3M, but is most preferably about 0.3M.
  • Nitric acids are avail ⁇ able in various grades, but it is preferred to use very pure nitric acids as obtainable from J.
  • an amount of separation ready source "cow” is then contacted with about an equal amount of separation ready organic extractant for the solvent extraction step, wherein the amount is from about 3 mL to about 10 ml * .
  • the solvent extraction is carried out by contacting (using a glass-covered stir bar and magnetic stir motor) the separation ready organic extractant with the separation ready source for a time of from about 5 minutes (min.) to about 30 in. , but preferably about 5 min. , to allow the separation ready source to reach equilibrium with the separation ready organic extractant, thereby allowing the separation ready organic extractant to extract the Y-90 from the separation ready source mixture, leaving an organic phase containing Y-90 and an aqueous phase retaining Sr-90.
  • the organic phase containing Y-90 which is immiscible with the remaining aqueous Sr-90 phase, is allowed to separate for a time of from about 15 min. to about 30 min. , but preferably about 15 min. , to ensure thorough separation of organic and aqueous phases. Finally, the organic phase containing Y-90 (about 9 mL) is decanted from the remaining Sr-90.
  • the remaining Sr-90 is an aqueous Sr-90 source or "cow" having very little Y-90 and containing traces of organic extractant left from the decanting step.
  • the aqueous Sr-90 "cow” is scrubbed twice using hexane. An amount of hexane from about 3 mL to about 6 mL, but preferably about 3 mL, is mixed with the aqueous Sr-90 "cow” to remove traces of the organic extractant. After removal of the second hexane scrub, the aqueous Sr-90 "cow” is dried to remove any remaining hexane. After drying, the Sr-90 "cow” is ready for storage and ingrowth of Y-90. Hexane is available in various grades, but it is preferred to use very pure hexane as obtainable from chemical suppliers; for example, Spectro Grade Hexanes, Reagent ACS, Catalog No. 1170034.
  • the organic extractant (about 9 mL) contains Y-90 and traces of Sr-90 impurity.
  • Purified Y-90 product is obtained in four steps, (1) at least two nitric acid scrubs, (2) at least one nitric acid strip, (3) at least one hexane scrub, and (4) at least one boildown to dryness.
  • the organic extractant is scrubbed two or three times with dilute nitric acid.
  • Each nitric acid scrub comprises mixing approximately equal volumes of organic extractant containing Y-90 and dilute nitric acid, wherein the volumes may range from about 8 mL to about 9 mL, but preferably are about 9 mL, having a preferred concentration of about 0.3M.
  • the nitric acid is mixed with the organic extractant for a time from about 5 min. to about 30 min. , but with 5 min. preferred. It is further preferred to stir the mixture during this time with a magnetic stirrer and a glass- covered stir bar. Between each scrub and after the last scrub, the mixture is allowed to separate into organic and aqueous phases for a time from about 5 min. to about 15 min., with 5 min. preferred. The aqueous phase con ⁇ taining traces of Sr-90 impurity is removed.
  • the scrubbed organic extractant containing the Y-90 product is further subjected to one to three nitric acid strips.
  • Each nitric acid strip comprises mixing approx ⁇ imately equal volumes of scrubbed organic extractant con ⁇ taining Y-90 and concentrated nitric acid, wherein the volumes may range from about 5 mL to about 9 mL, but preferably about 5 mL.
  • the concentration of concentrated nitric acid is preferably about 7M.
  • the mixture is allowed to separate into organic and aqueous phases for a time from about 5 min. to about 15 min. , with 5 min. preferred.
  • the aqueous phase containing Y-90 is collected.
  • the aqueous phase containing Y-90 is then mixed with one to three hexane scrubs to further remove traces of organic extractant from the Y-90.
  • the amount of hexane is preferred to be about 10 ml for about 18 ml of stripped product.
  • the amount of hexane may range from about 3 mL to about 9 mL. With lesser amounts of hexane, more scrubs are needed.
  • Hexane may be in contact with the Y-90 for times ranging from about 5 min. to about 30 min., but it is preferred that the contact time is about 5 min.
  • Boiling may be done in any container, but is preferably done in a closed container, preferably a plastic tube, and most preferably a polytetrafluroethylene (e.g., Teflon) tube.
  • a closed container preferably a plastic tube, and most preferably a polytetrafluroethylene (e.g., Teflon) tube.
  • the dried Y-90 product may be further placed back in solution according to end-use specifications.
  • the dry product may be dissolved into solution by adding concentrated hydrochloric acid to the dry product while it is hot.
  • the amount of hydrochloric acid may be from about 0.1 mL to about 1 mL, but preferably about 0.3 mL of a concentration from about 7M to about 10M, but most preferably about 8M.
  • One or two, preferably two, additional volumes of about 0.3M hydrochloric acid are used to wash the Y-90 product from the heating container (Teflon tube) into a collection container, preferably a V-bottom vial.
  • Hydrochloric acids are available in various grades, but it is preferred to use very pure hydrochloric acids as obtainable from J. T. Baker, Inc., as ULTREX Ultrapure reagents.
  • the product solution in the V- bottom vial may be treated for delivery in one of two product treatments.
  • the product In a first product treatment, the product may be dried then brought into a customer speci ⁇ fied hydrochloric acid solution concentration (usually about 0.3M HC1) , or in a second product treatment the product may be passed through an ion exchange then dried and put into a hydrochloric acid solution concentration (of customer choice) .
  • the Y-90 product is dried then dissolved in hydrochloric acid.
  • the amount of hydrochloric acid may range from about 0.1 mL to about 1.0 mL, and the concentration of hydrochloric acid may range from about 0.1M to about 1.0M, but is preferably about 0.3M.
  • the Y-90 product is dried and dissolved in hydrochloric acid.
  • the amount of hydrochloric acid may range from about 0.3 mL to about 1.0 mL, preferably about 0.5 mL, and the concentration of hydrochloric acid may range from about 7M to about 9M, but is preferably about 7M.
  • the hydrochloric acid containing Y-90 is trans ⁇ ferred to an ion-exchange column for removal of any traces of iron (and other metals) .
  • the ion-exchange column contains an amount of resin from about 100 mg to about 400 mg, but preferably about 140 mg.
  • the preferred ion-exchange resin is chloride form anion-exchange resin, and more preferably an AG-1, 4X, 200-400 mesh ion- exchange resin or equivalent available from Bio-Rad. After the ion exchange, the resin is washed one or two times with hydrochloric acid of about 7M in an amount of about 0.5 mL.
  • the hydro ⁇ chloric acid containing Y-90 is dried by heating. While the dry Y-90 is hot, an amount of dilute hydrochloric acid is added where the amount is from about 0.1 mL to about 1.0 mL, having a concentration from about 0.05M to about 0.3M, but preferably about 0.05M. Heating is continued for a time from about 5 min. to about 30 min. , but preferably about 15 min. to bring the dry Y-90 product into solution.

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Abstract

L'invention se rapporte à un procédé de purification à partir d'une source Sr-90/Y-90; la source brute Sr-90/Y-90 contenant des impuretés est obtenue à partir d'un retraitement nucléaire des matériaux. La source brute Sr-90/Y-90 est purifiée en une source fraîche Sr-90/Y-90 en éliminant les impuretés par ajout d'hydroxyde de sodium, et en retirant Cs-137 par un autre ajout de carbonate de sodium. La source fraîche est mise de côté pour permettre la croissance interne. Un produit d'épuisement organique HDEHP est obtenu dans le commerce, et est ensuite purifié par saturation avec Cu(II), par précipitation avec l'acétone, et par lavage avec l'acide nitrique. La source fraîche est ensuite dissoute dans l'acide nitrique et le HDEHP purifié est lavé et nettoyé à l'acide nitrique. La source fraîche dissoute et le HDEHP nettoyé sont associés dans une extraction organique, séparant Y-90 de Sr-90, avec un rapport de concentration Sr-90/Y-90 ne dépassant pas 10(E-7), et une concentration d'impuretés métalliques ne dépassant pas 10 ppm par curie de Y-90. Y-90 séparé peut ensuite être préparé pour être distribué.
PCT/US1993/004282 1992-05-08 1993-05-05 Procede destine a separer l'yttrium-90 du strontium-90 Ceased WO1993023854A1 (fr)

Applications Claiming Priority (2)

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US88096192A 1992-05-08 1992-05-08
US07/880,961 1992-05-08

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2155399C1 (ru) * 1999-04-01 2000-08-27 РНЦ "Курчатовский институт" Способ получения радиоизотопа стронций-89
RU2155398C1 (ru) * 1999-02-23 2000-08-27 РНЦ "Курчатовский институт" Способ получения радиоизотопа стронций-89
US6309614B1 (en) * 2000-04-14 2001-10-30 Pg Research Foundation, Inc. Method for isolating and purifying 90Y From 90strontium in multi-curie quantities
RU2177909C1 (ru) * 2000-08-18 2002-01-10 Государственный научный центр - Государственный научно-исследовательский институт атомных реакторов СПОСОБ ВЫДЕЛЕНИЯ РАДИОНУКЛИДА Sr-89 БЕЗ НОСИТЕЛЯ ИЗ ОБЛУЧЕННОГО ИТТРИЯ
RU2187336C1 (ru) * 2001-06-01 2002-08-20 Государственное унитарное предприятие Государственный научный центр Российской Федерации Физико-энергетический институт им. акад. А.И.Лейпунского Способ получения препарата на основе стронция-89
RU2307071C2 (ru) * 2005-11-25 2007-09-27 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации - Физико-энергетический институт им. А.И. Лейпунского" Способ производства стронция-90 без носителя и стронция-89 без носителя с использованием ядерного водно-растворного реактора и устройство для реализации способа
RU2307072C2 (ru) * 2005-11-25 2007-09-27 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации - Физико-энергетический институт им. А.И. Лейпунского" Способ производства стронция-90 без носителя с использованием ядерного водно-растворного реактора и устройство для реализации способа
RU2312816C2 (ru) * 2006-01-10 2007-12-20 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации-Научно-исследовательский институт атомных реакторов" Способ отделения стронция-89 от иттрия

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
APPL.RADIAT.ISOTOP. vol. 41, no. 9, 1990, GB pages 861 - 865 WIKE ET AL. 'CHEMISTRY FOR COMMERCIAL SCALE PRODUCTION OF YTTRIUM-90 FOR MEDICAL RESEARCH.' cited in the application *
DATABASE INIS AN 23(3):6797 STUDY ON THE SEPARATION OF CARRIER-FREE YTTRIUM-90 FROM STRONTIUM-90 *
DATABASE WPI Derwent Publications Ltd., London, GB; AN 84-079825 *
J.INORG.NUCL.CHEMISTRY vol. 31, 1969, GB pages 2587 - 2589 PARTRIDGE ET AL. 'PURIFICATION OF DI-(2-ETHYLHEXYL)PHOSPHORIC ACID BY PRECIPITATION OF COPPER(II) DI-(2-ETHYLHEXYL)PHOSPHATE.' cited in the application *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2155398C1 (ru) * 1999-02-23 2000-08-27 РНЦ "Курчатовский институт" Способ получения радиоизотопа стронций-89
RU2155399C1 (ru) * 1999-04-01 2000-08-27 РНЦ "Курчатовский институт" Способ получения радиоизотопа стронций-89
US6309614B1 (en) * 2000-04-14 2001-10-30 Pg Research Foundation, Inc. Method for isolating and purifying 90Y From 90strontium in multi-curie quantities
RU2177909C1 (ru) * 2000-08-18 2002-01-10 Государственный научный центр - Государственный научно-исследовательский институт атомных реакторов СПОСОБ ВЫДЕЛЕНИЯ РАДИОНУКЛИДА Sr-89 БЕЗ НОСИТЕЛЯ ИЗ ОБЛУЧЕННОГО ИТТРИЯ
RU2187336C1 (ru) * 2001-06-01 2002-08-20 Государственное унитарное предприятие Государственный научный центр Российской Федерации Физико-энергетический институт им. акад. А.И.Лейпунского Способ получения препарата на основе стронция-89
RU2307071C2 (ru) * 2005-11-25 2007-09-27 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации - Физико-энергетический институт им. А.И. Лейпунского" Способ производства стронция-90 без носителя и стронция-89 без носителя с использованием ядерного водно-растворного реактора и устройство для реализации способа
RU2307072C2 (ru) * 2005-11-25 2007-09-27 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации - Физико-энергетический институт им. А.И. Лейпунского" Способ производства стронция-90 без носителя с использованием ядерного водно-растворного реактора и устройство для реализации способа
RU2312816C2 (ru) * 2006-01-10 2007-12-20 Федеральное государственное унитарное предприятие "Государственный научный центр Российской Федерации-Научно-исследовательский институт атомных реакторов" Способ отделения стронция-89 от иттрия

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