IL29607A - Production of high purity radioactive technetium-99m - Google Patents

Production of high purity radioactive technetium-99m

Info

Publication number
IL29607A
IL29607A IL29607A IL2960768A IL29607A IL 29607 A IL29607 A IL 29607A IL 29607 A IL29607 A IL 29607A IL 2960768 A IL2960768 A IL 2960768A IL 29607 A IL29607 A IL 29607A
Authority
IL
Israel
Prior art keywords
technetium
slurry
molybdenum
sterile
oxidized
Prior art date
Application number
IL29607A
Original Assignee
Union Carbide Corp
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 Union Carbide Corp filed Critical Union Carbide Corp
Publication of IL29607A publication Critical patent/IL29607A/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C22METALLURGY; FERROUS OR NON-FERROUS ALLOYS; TREATMENT OF ALLOYS OR NON-FERROUS METALS
    • C22BPRODUCTION AND REFINING OF METALS; PRETREATMENT OF RAW MATERIALS
    • C22B61/00Obtaining metals not elsewhere provided for in this subclass
    • GPHYSICS
    • G21NUCLEAR PHYSICS; NUCLEAR ENGINEERING
    • G21GCONVERSION OF CHEMICAL ELEMENTS; RADIOACTIVE SOURCES
    • G21G1/00Arrangements for converting chemical elements by electromagnetic radiation, corpuscular radiation or particle bombardment, e.g. producing radioactive isotopes
    • G21G1/0005Isotope delivery systems

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  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Manufacturing & Machinery (AREA)
  • Materials Engineering (AREA)
  • Mechanical Engineering (AREA)
  • Metallurgy (AREA)
  • Organic Chemistry (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Description

Patents Form No. 3 PATENTS AND DESIG S ORDINANCE.
SPECIFICATION.
"PROOUCTIOH OF HIGH FORITY RADIOACTIVE TKCHHBTHm-99m,f «nfmi jroi va »:j*si{?in»vi 399-01* ewaao τί*"« I / WE , UHXOH CARBXDS CORiwmTIOB,...jof ..57B-Papk-Aventtet under the law© of th© State of New York, United states of America, do hereby declare the nature of this invention and in what manner the same is to be performed, to be particularly described aud ascertained in and by the following statement : - This invention relates to a novel process for the production of radioaotive technetium-99m. In one aspect, this invention relates to a novel process for the production of radioactive technetium-99m in high yields. A further aspect of this invention is directed to a novel process for the production of radioaotive technetium-99m which can be obtained in a high degree of purity.
Recent medical investigation has shown that technetium-99m is an extremely useful tool for diagnosis. High purity technetium-99m is used primarily as a radioisotope in a variety of medical research and diagnosis. It is well suited for liver, lung, blood pool and tumor scanning, and is preferred over other radioactive isotopes because of its short half-life which results in reduced exposure of the organs to radiation.
In addition to medical uses, technetium-99m can also' be employed in industrial applications, such as in the measurement of flow rates, process control, radiometric chemistry, and the like. Since the radioisotope sought to be used has such a short half-life, it is common practice to ship the users of the isotope the parent element; in this case radioactive molybdenum-99. The user then extracts the technetium from the molybdenum-99 as his needs require.
In the past, radioactive technetium-99m has been produced by a variety of methods. For example, M.S. Faddeeva et al., Zhur. Neorg. Khim. , 3, 165-166 (1958), has disclosed a process for extracting technetium-99m from 6N aqueous K2CO3 solutions containing dissolved molybdenum-99 containing material, using methyl ethyl ketone as the extracting medium, followed by washing the ketone solutions with KgCOg aqueous solution. The teohnetium-99«n recovered by this process, however, was not pure, since the product contained detectable K2C0g and would therefore not be useable for many purposes, such as for medical purposes.
More recently, a process was perfected for the separation of technetium-99m from molybdenura-99. Separation vrae effected by contacting the molybdenum-99 (in the form of molybdate ions) with alumina, followed by selective removal of technetium-99m (in the form of TcC -ion) from the bonded alumina. Although, to date, the alumina column generally is acceptable, the chemical purity of the eluant barely meets minimum medical requirements and the column itself is at times unstable, producing an eluant unfit for medical purposes.
Finally, J. J. Pinajian, International J. Applied Radioactive Isotopes, 1£, 664 (1966) reported a method which used hydrous zirconium oxide as the absorbing media for the chromatographic selective adsorption of molybdenum and eluded technetium-99m with acid methyl ethyl ketone (5 vol. # 0.01 MHC1). The methyl ethyl ketone eluant must then be processed to produce a physiologically acceptable solution for parental injection because of its extreme toxicity.
It is therefore an object of this invention to provide a more efficient method for producing radioactive technetium-99m. Another object of this invention is to provide a process for preparing radioactive technetium-99m in a high degree of purity and by an extremely reproducible process. A further object of this invention is to provide a process which avoids the need for separating radioactive products and other impurities. These and other objects will readily become apparent to those skilled in the art in the light of the teachings herein set forth.
It has now been discovered that the aforementioned objects can be achieved by a process which comprises the steps of (a) producing radioactive mblybdenum-99, (b) dissolving the radioactive compound, (c) adjusting the pH of the radioactive hydrous zirconium oxide, and (e) selectively extracting technetium-99m from the oxidized substrate.
Operating in the aforesaid manner provides a selective separation of technetium-99m from all other elements in the dissolved radioactive molybdenum-99 compound with very high efficiency, i.e., over 80 per cent.
In addition the process of this invention is readily reproducible and simple to operate.
Although a variety of compounds are suitable for use in the process of this invention the preferred target is molybdenum trioxide. In the event that other compounds are employed, it is often necessary- to isolate the molybdenum component after irradiation. Illustrative compounds which can be employed as the source of molybdenum-99 include, among others, molybdenum metal, molybdenum nitrate, molybdenum sulfate, organic molybdenum compounds such as molybdenum acetylacetonates, and fissionable materials such as uranium- 235 » uranium-238, plutonium- 239 , and the like.
Irradiation of compounds to produce molybdenum-99 Is a well known technique and can be effected by placing the proper compound in the irradiation zone of a nuclear reactor, particle generator, or neutron isotopic source.
Thereafter, the irradiated compound is dissolved in a suitable solvent. In the case of molybdenum trioxide it may be necessary to employ a basic solvent such as sodium hydroxide, ammonium hydroxide, and the like, the techniques to dissolve and isolate a pure molybdenum-99 solution are well known in the art.
In contrast to the work disclosed by Pinajian, wherein hydrous zirconium oxide was employed, it has now been unexpectedly and surprisingly found that when a zirconium salt, such as hydrous zirconium oxide, is contacted with an selectively adsorbs molybdenum but does not appear to adsorb technetium. It is also surprising that ^ (a) the loading capacity of the system exceeds all other known systems which yielc". equivalent amounts of technetium when using physiological saline, (b) that the saline containing the technetium product has unexpectedly lower elemental impurities due to the molybdenum absorbing substrate, and (c) that the saline contains appreciably more technetium and less molybdenum than comparable systems heretofore known.
In accordance with the process of the present invention molybdenum solution, such as aqueous ammonium molybdate is contacted with oxidized zirconium salts. The oxidized zirconium salts are prepared by contacting a compound, such as hydrous zirconium oxide, with an oxidizing agent, in the presence of an acid. Suitable oxidizing agents which can be employed include, among others, bromine water, chlorine water, iodide water, permanganate salts, such as potassium permanganate, chlorate salts, such as potassium chlorate, hydrogen peroxide, organic peroxides, such as benzoyl peroxide and the like.
Thereafter, the pH of the contacted solution is adjusted to a range between 2 to 7 and more preferably between 3.5 and 6.0. Normally, it is preferable to heat the solution during pH adjustment and control and to maintain this heat for a duration of approximately twenty minutes to insure adsorption of the molybdenum on the zirconium substrate. Temperature is not necessarily critical and need only be sufficient to insure complete reaction of the molybdenum and the oxidized zirconium salt. In practice, temperatures greater than 70°C, have been found satisfactory, with the preferred temperature being The zirconium substrate containing the molybdenum is then transferred to an appropriate elution system such as a column, or vessel, preferably glass, or other inert material. The supernatant liquid is allowed to drain or removed by filtration or decantation and the substrate washed with isotonic saline.
The technetium-99m in the column or vessel which contains 99Mo-99mTc activity can subsequently be isolated, e.g., milked, filtered, centrifuged or the like for technetium-99m as it is formed with an acidic, neutral or basic solution. Preferably, it has been observed that best results are obtained when the system is eluted with 20 milliliter portions of isotonic saline solutions. This is done by contacting the substract with the desired volume of saline and collecting the liquid portion.
Numerous variations of the preferred embodiment described above may be practiced, as will be apparent to those skilled In the art, without departing from the basic concepts of the present invention.
As previously indicated, the process of the present invention provides a simple method for the preparation of technetium-99m in a high degree of efficiency. By this process recovery of technetium-99m can be effected with isotonic saline in efficiencies as high as 95 and higher, over a pH range of about 4.0 to about 7.0 without appreciable dissolution of the zirconium substrate or removal of any molybdenum from the zirconium substrate.
A further advantage characteristic of the process of this invention, is that the substrate and/or the entire elution system can be sterilized, i.e., by autoclaving at the normally prescribed temperatures and pressures.
In contrast, the previously known hydrous zirconium oxide, which are loaded with an acid solution containing molybdenum can not be efficiently eluted for technetium with isotonic saline.
The following example is illustrative: EXAMPLE 1 To 100 grams of Bio Rad hydrous zirconium oxide (100-200 mesh) was added 100 milliliters of 0.1 MHC1 and 10 milliliters of saturated bromine water. The mixture was stirred and allowed to stand for 10 minutes. Thereafter 15 milliliters of 1 M NaOH was added to the slurry. A sufficient volume of this slurry was transferred into a 150 milliliter beaker to provide 1 milliliter of slurry per 57 milligrams of molybdenum.
Thereafter the slurry was washed three times with water and four drops of saturated bromine water added. To the slurry was added a solution containing 1 gram of irradiated molybdenum material as the molybdate in 20 milliliters of 20 per cent ammonium hydroxide. The mixture was heated with stirring and 6M HNO3 was slowly added until pH was between 4 to 6. Additional HNO3 was added to maintain this pH until the chemical reaction was complete. Thereafter, the slurry was heated for 20 minutes and cooled. The slurry was then transferred into a column and washed with isotonic saline solution. After the technetium-99m had built up in the generator it was eluted with isotonic saline solution.
The column was tested for molybdenum break-through by radiometric analysis and no molybdenum-99 was observed.
Chemical purity was tested by emission spectroscopy for the major elements of the column substrate, i.e., zirconium, and none was detectable.
EXAMPLE 2 A comparison of adsorption-elution characteristics with a recent method, wherein an alumina column 18 employee the data obtained is set forth in Table I below: TABLE I COMPARISON OP ADSORPTION-ELUTION CHARACTERISTICS OF ZIRCO IA AND ALUMINA SYSTEMS Alumina Zlrconia Mo loading (mg Mo/ml adsorber) < 2 >57 99mTc Recovery (#) in isotonic saline solution sterile 60-80/30 ml > 9Ο/3Ο ml non-sterile 80/20 ml >80/20 ml metal impurity (ppm) sterile >1 <1 non-sterile >50 <1 stability fair excellent As previously indicated radiometric analysis of the eluted technetium-99m indicates that it contains up to 95 per cent of the available technetium-99m and the radionuclidic purity is greater thar 99.99 per jent. The total metal element impurity is less than 1 p rt per million as determined by emission spectroscopy techniques.
The substrate and/or the entire elution system can be sterilized b acceptable autoclave techniques with no reduction in radionuclidic impurity, no increase in the metal element impurities and no reduction in the amount of technetium-99m recoverable.
Although the invention has been illustrated by the preceding example, it is not to be construed as being limited to the materials employed therein, but rather, the invention encompasses the generic area as hereinbefore disclosed. Various modifications and embodiments of this invention can be made without departing from the spirit and scope thereof.

Claims (11)

HAVING NOW particularly described and ascertained the nature * of our said invention and in what manner the same same is to be performed, we declare that what we claim is s
1. A process for producing radioactive teohnetium-99m which comprises the steps of: (a) contacting an oxidized zirconium salt with a solution containing radioaotlve molybdenum 99; to produce a slurry; (b) adjusting and maintaining the pH of said slurry to within the range of from 2 to 7; (c) heating said slurry above 40eC. until etatio conditions of pH are observed; (d) selectively extracting said slurry with a solvent to separate technetium-99m from its radioactive parent molybdenum-99 that is deposited on the slurry.
2. The process of claim 1 wherein said oxidized zirconium salt is oxidized hydrous zirconium oxide.
3. The process of claim 2 wherein said oxidized hydrous zirconium oxide is obtained by contacting hydrous zirconium oxide with an oxidizing agent.
4. The process of claim 3 wherein said oxidizing agent is selected from the group consisting of bromine water, chlorine water, iodine water, potassium permanganate, potassium chlorate, hydrogen peroxide, and benzoylperoxide.
5. The process of claim 3 wherein said oxidizing agent is bromine water.
6. The process of claim 1 wherein technetium-99m is selectively extracted with Isotonic saline.
7. The process of claim 1 wherein said slurry is 29607/2 '·
8. The process of claim 7 wherein said sterile slurry is extracted with sterile isotonic saline to provide a sterile solution containing technetium-99m.
9. A sterile, isotonic saline solution consisting of technetium-99m and having a radionuclidlc purity greater than 99.99 percent and a total metal element impurity of less than 1 part per million.
10. The process of claim 1 wherein technetium-99m is selectively extracted with methyl ethyl ketone.
11. The process of claim 1 wherein technetium-99m is selectively extracted with an aqueous solution of an inorganic acid. Attorney for Applicants.
IL29607A 1967-06-16 1968-03-08 Production of high purity radioactive technetium-99m IL29607A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US64645367A 1967-06-16 1967-06-16

Publications (1)

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IL29607A true IL29607A (en) 1971-10-20

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Application Number Title Priority Date Filing Date
IL29607A IL29607A (en) 1967-06-16 1968-03-08 Production of high purity radioactive technetium-99m

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US (1) US3468808A (en)
BE (1) BE716569A (en)
DE (1) DE1758118C3 (en)
FR (1) FR1561828A (en)
GB (1) GB1207246A (en)
IL (1) IL29607A (en)
NL (1) NL6804929A (en)
SE (1) SE350954B (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL165321C (en) * 1971-03-02 1981-03-16 Byk Mallinckrodt Cil Bv METHOD FOR THE MANUFACTURE OF A RADIO ISOTOPE GENERATOR GENERATOR.
US4010109A (en) * 1973-07-02 1977-03-01 Kurt Sauerwein Device for marking fluent materials
US4158700A (en) * 1976-03-08 1979-06-19 Karageozian Hampar L Method of producing radioactive technetium-99M
US4280053A (en) * 1977-06-10 1981-07-21 Australian Atomic Energy Commission Technetium-99m generators
US4206358A (en) * 1977-10-19 1980-06-03 Australian Atomic Energy Commission Technetium-99 generators
US8449850B2 (en) * 2010-02-19 2013-05-28 Babcock & Wilcox Technical Services Group, Inc. Method and apparatus for the extraction and processing of molybdenum-99
GB201112051D0 (en) * 2011-07-13 2011-08-31 Mallinckrodt Llc Process
EP2862181B1 (en) 2012-06-15 2017-04-19 Dent International Research, Inc. Apparatus and methods for transmutation of elements
US9842664B2 (en) 2013-09-26 2017-12-12 Los Alamos National Security, Llc Recovering and recycling uranium used for production of molybdenum-99
US9793023B2 (en) 2013-09-26 2017-10-17 Los Alamos National Security, Llc Recovery of uranium from an irradiated solid target after removal of molybdenum-99 produced from the irradiated target
WO2016022848A1 (en) * 2014-08-06 2016-02-11 Research Triangle Institute High efficiency neutron capture products production
US20180244535A1 (en) * 2017-02-24 2018-08-30 BWXT Isotope Technology Group, Inc. Titanium-molybdate and method for making the same
AR115584A1 (en) * 2018-06-20 2021-02-03 Bwxt Isotope Tech Group Inc SYSTEM AND METHOD FOR EVALUATING THE EVALUATION EFFECTIVENESS AND RADIOPURITY OF Tc-99m GENERATORS
JP6554753B1 (en) * 2019-03-11 2019-08-07 株式会社京都メディカルテクノロジー Technetium 99m isolation system and technetium 99m isolation method
CN114121330B (en) * 2021-11-11 2024-05-14 中国核动力研究设计院 Molybdenum technetium generator, preparation method and device

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB896758A (en) * 1959-11-13 1962-05-16 Atomic Energy Authority Uk Improvements in or relating to the separation of technetium from fission product solutions

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DE1758118B2 (en) 1973-10-18
NL6804929A (en) 1968-12-17
GB1207246A (en) 1970-09-30
DE1758118C3 (en) 1974-05-30
SE350954B (en) 1972-11-13
DE1758118A1 (en) 1970-12-23
FR1561828A (en) 1969-03-28
BE716569A (en) 1968-12-16
US3468808A (en) 1969-09-23

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