EP0575531A1 - Method of improving the elution yield of a radioisotope generator - Google Patents

Method of improving the elution yield of a radioisotope generator

Info

Publication number
EP0575531A1
EP0575531A1 EP19920908946 EP92908946A EP0575531A1 EP 0575531 A1 EP0575531 A1 EP 0575531A1 EP 19920908946 EP19920908946 EP 19920908946 EP 92908946 A EP92908946 A EP 92908946A EP 0575531 A1 EP0575531 A1 EP 0575531A1
Authority
EP
European Patent Office
Prior art keywords
generator
eluent
air
reservoir
inlet opening
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.)
Withdrawn
Application number
EP19920908946
Other languages
German (de)
French (fr)
Inventor
Harm M. Mallinckrodt Medical B.V. Benjamins
Mathijs Mallinckrodt Medical B.V. Kroon
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mallinckrodt Inc
Original Assignee
Mallinckrodt Medical 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 Mallinckrodt Medical Inc filed Critical Mallinckrodt Medical Inc
Priority to EP19920908946 priority Critical patent/EP0575531A1/en
Publication of EP0575531A1 publication Critical patent/EP0575531A1/en
Withdrawn legal-status Critical Current

Links

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

Definitions

  • the present invention relates to a method of improving the elution yield of a radioisotope generator, comprising a column containing carrier material adapted to adsorb a parent isotope, said column including an inlet opening and an outlet opening, said outlet opening being connected via an eluate conduit to a tapping point, where a liquid eluate containing a daughter radioisotope can be obtained, said inlet opening being connected via an eluent conduit to an eluent reservoir, said reservoir being provided with an inlet opening for air suppletion to the generator during elution thereof.
  • Radioisotope generators are devices used in obtaining a solution of a daughter radioisotope such as technetium-99m from an adsorbed parent radioisotope such as molybdenum-99 which produces the daughter radioisotope upon radioactive decay.
  • the solution of the daughter radioisotope may be used for radiodiagno ⁇ tic purposes.
  • radioisotope generators include a column containing the parent radioisotope adsorbed on a carrier material such as an anion exchange medium or another medium such as alumina which has a relatively high adsorptive capacity for the parent radioisotope but a relatively low adsorptive capacity for the daughter radioisotope.
  • a carrier material such as an anion exchange medium or another medium such as alumina which has a relatively high adsorptive capacity for the parent radioisotope but a relatively low adsorptive capacity for the daughter radioisotope.
  • the column is eluted by washing with a suitable solvent or eluent such as a saline solution.
  • the resulting eluate containing the daughter radioisotope in the form of a dissolved salt is useful as a diagnostic agent, for example, and can then be used for intravenous administration.
  • a reservoir containing a quantity of eluent can be connected to the inflow side of the column and an evacuated elution vial can be connected to the outflow side of the column at a tapping point on the generator.
  • the vacuum in the vial draws the eluent from the reservoir, through the column and into the vial, thereby eluting the daughter radioisotope from the column.
  • the present invention relates to a method of improving the elution yield of a radioisotope generator, as described above, wherein the column of the radioisotope generator contains a carrier material which at least substantially consists of alumina, wherein the parent isotope is molybdenum-99, wherein the daughter isotope is technetium-99m, and wherein the eluent is a saline solution, preferably a physiological saline solution.
  • the eluate produced by such a Mo99-Tc99m generator can indeed be used directly as a diagnostic agent and can then be administered intravenously to enable imaging of the organ or of the pathological process in which the radioactivity has been accumulated (scanning) .
  • the eluate is not suitable for selective radioactive labelling of the target organ or tissue.
  • labelled substances such as phosphonates, colloids, complex-forming ligands, peptides and biological macromolecules, e.g. proteins, etc.
  • the eluate of a Mo99-Tc99m generator is usually adapted for the labelling of suitable substances.
  • Such a labelling procedure is generally so simple, that the user can perform his or her own labelling reaction in the clinic or clinical laboratory.
  • the substance to be labelled can be at the user's disposal in the form of a so- called cold kit.
  • the eluate can easily be obtained by the user from the Mo99-Tc99m generator available for this purpose.
  • a Mo99-Tc99m generator for the above purposes, wherein the column contains as a carrier material alumina provided with a small content of hydrated manganese dioxide.
  • a generator is disclosed e.g. in U.S. patent 3,970,583.
  • the hydrated managanese dioxide present on the carrier material normally has a favourable influence on the elution yield, viz. generally the elution yield is improved and fluctuations in the elution yield are avoided by applying such a modified alumina as a carrier material.
  • the eluate thus obtained may contain several impurities which cause problems, in particular when used for the labelling of certain substances as defined above. These labelling problems are expressed in low and/or fluctuating labelling yields.
  • unmodified alumina as a carrier material for the column of a radioisotope generator. Indeed, this has a favourable effect on the labelling yield, but in practice the improvement is not sufficient, because it results in irreproducible elution yields of the generator.
  • This object can be achieved according to the present invention, in that during elution of the generator air is supplied to the eluent reservoir, which air has a minimized alcohol content.
  • Alcohol, in particular propanol may be employed during assemblage of the generator and is usually employed in a clinic or clinical laboratory for cleaning and sterilizing purposes.
  • the method is in particular applicable to a Mo99-Tc99m generator, i.e. a radioisotope generator of which the column contains a carrier material which at least substantially consists of alumina, wherein the parent isotope is molybdenum-99, wherein the daughter isotope is technetium-99m, and wherein the eluent is a saline solution, preferably a physiological saline solution. It has been observed, that by using the method of the present invention, a high and constant elution yield is guaranteed during the whole elution period, even when unmodified alumina is used as a carrier for the parent isotope molybdenum-99.
  • the extent to which the alcohol content in the air to be supplied to the eluent reservoir should be reduced depends on the frequency of use of the generator and consequently on the quantity of supplied air per time unit.
  • the alcohol content of the air to be supplied should be reduced to such an extent, that the alcohol concentration in the eluent never can reach a value of 0.1 ⁇ 1/ml, preferably of 0.05 /.I/ml. This will be demonstrated in a model example attached.
  • a suitable filter means for this purpose is an active-carbon filter, either in the form of active-carbon granules contained in a filter housing, or in the form of an active-carbon filter plate framed in a holder.
  • the present invention also relates to a radioisotope generator as defined hereinbefore, said generator being characterized in that it comprises filter means suitable for reducing the alcohol content of the air to be supplied to the eluent reservoir during elution of the generator.
  • a suitable filter means comprises an active carbon filter, as stated above.
  • the filter means is preferably sealingly connected to the inlet opening of the eluent reservoir to avoid any inward leakage of alcohol-contaminated air during elution. Normally the inlet opening of the eluent reservoir is equally provided with a bacteria filter to keep the generator in a sterile condition.
  • the filter means to be used according to the invention is connected between the eluent reservoir and the bacteria filter.
  • Propanol in an amount of 0.5 ml, is introduced under the elution cover of a radioisotope generator, so in the proximity of the inlet opening of the eluent reservoir.
  • the Mo99-Tc99m generator used has been provided with an unmodified Al 0 3 -packed column. After the second elution another 0.5 ml quantity of propanol is introduced under the elution cover of the generator.
  • Table B both in the absence and in the presence of an active-carbon filter.
  • FIG. 1 The holder shown in Fig. 1 is adapted to accommodate active- carbon granules.
  • This holder comprises a filter housing 10, to the upper edge of which a cover 11 has been clamped, both parts being manufactured from a synthetic material.
  • the housing is provided with a means for a sealing connection to the inlet opening of the eluent reservoir of a radioisotope generator.
  • This connection means is formed as a luer lock cone 12 and is integrated with the housing of the holder. The cover can be removed from the housing to allow the holder to be filled with active-carbon granules.
  • the air to be supplied to the eluent reservoir is admitted to the holder through the bores 13, recessed in the cover, passes the active-carbon granules and leaves the housing through a bore 14, provided in the bottom thereof.
  • the holder further comprises a centring skirt 15 and strengthening ribs 16.
  • the holder 20 shown in Fig. 2 is adapted to accommodate an active-carbon filter plate to be clamped within the holder between the upper (21) and lower (22) edges thereof.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • High Energy & Nuclear Physics (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Saccharide Compounds (AREA)

Abstract

Procédé d'amélioration du rendement d'élution d'un générateur radio-isotopique par l'introduction d'air dans son réservoir à éluant pendant l'élution du générateur, lequel air présente une teneur minimisée en alcool. On a également prévu un générateur radio-isotopique comportant un dispositif de filtrage apte à réduire la teneur en alcool de l'air à introduire.Method for improving the elution yield of a radioisotopic generator by introducing air into its eluent reservoir during the elution of the generator, which air has a minimized alcohol content. A radioisotopic generator is also provided, comprising a filtering device capable of reducing the alcohol content of the air to be introduced.

Description

Method of improving the elution yield of a radioisotope generator.
The present invention relates to a method of improving the elution yield of a radioisotope generator, comprising a column containing carrier material adapted to adsorb a parent isotope, said column including an inlet opening and an outlet opening, said outlet opening being connected via an eluate conduit to a tapping point, where a liquid eluate containing a daughter radioisotope can be obtained, said inlet opening being connected via an eluent conduit to an eluent reservoir, said reservoir being provided with an inlet opening for air suppletion to the generator during elution thereof.
Radioisotope generators are devices used in obtaining a solution of a daughter radioisotope such as technetium-99m from an adsorbed parent radioisotope such as molybdenum-99 which produces the daughter radioisotope upon radioactive decay. The solution of the daughter radioisotope may be used for radiodiagnoεtic purposes.
Conventionally, radioisotope generators include a column containing the parent radioisotope adsorbed on a carrier material such as an anion exchange medium or another medium such as alumina which has a relatively high adsorptive capacity for the parent radioisotope but a relatively low adsorptive capacity for the daughter radioisotope. To obtain the desired daughter radioisotope, the column is eluted by washing with a suitable solvent or eluent such as a saline solution. The resulting eluate containing the daughter radioisotope in the form of a dissolved salt is useful as a diagnostic agent, for example, and can then be used for intravenous administration. To obtain a quantity of the eluate from the generator in a simple and safe manner, a reservoir containing a quantity of eluent can be connected to the inflow side of the column and an evacuated elution vial can be connected to the outflow side of the column at a tapping point on the generator. The vacuum in the vial draws the eluent from the reservoir, through the column and into the vial, thereby eluting the daughter radioisotope from the column.
More in particular, the present invention relates to a method of improving the elution yield of a radioisotope generator, as described above, wherein the column of the radioisotope generator contains a carrier material which at least substantially consists of alumina, wherein the parent isotope is molybdenum-99, wherein the daughter isotope is technetium-99m, and wherein the eluent is a saline solution, preferably a physiological saline solution. The eluate produced by such a Mo99-Tc99m generator can indeed be used directly as a diagnostic agent and can then be administered intravenously to enable imaging of the organ or of the pathological process in which the radioactivity has been accumulated (scanning) . Generally, however, the eluate is not suitable for selective radioactive labelling of the target organ or tissue. For this purpose one needs labelled substances, such as phosphonates, colloids, complex-forming ligands, peptides and biological macromolecules, e.g. proteins, etc., having a large target organ specificity. Therefore, the eluate of a Mo99-Tc99m generator is usually adapted for the labelling of suitable substances. Such a labelling procedure is generally so simple, that the user can perform his or her own labelling reaction in the clinic or clinical laboratory. For this purpose the substance to be labelled can be at the user's disposal in the form of a so- called cold kit. The eluate can easily be obtained by the user from the Mo99-Tc99m generator available for this purpose.
It is common practice to use a Mo99-Tc99m generator for the above purposes, wherein the column contains as a carrier material alumina provided with a small content of hydrated manganese dioxide. Such a generator is disclosed e.g. in U.S. patent 3,970,583. The hydrated managanese dioxide present on the carrier material normally has a favourable influence on the elution yield, viz. generally the elution yield is improved and fluctuations in the elution yield are avoided by applying such a modified alumina as a carrier material. It has been observed, however, that by employing this usually applied carrier material in a Mo99-Tc99m generator, the eluate thus obtained may contain several impurities which cause problems, in particular when used for the labelling of certain substances as defined above. These labelling problems are expressed in low and/or fluctuating labelling yields. To avoid these problems, one has resorted to the use of unmodified alumina as a carrier material for the column of a radioisotope generator. Indeed, this has a favourable effect on the labelling yield, but in practice the improvement is not sufficient, because it results in irreproducible elution yields of the generator.
Consequently, the users of radioisotope generators continue to complain of the inexplicably fluctuating elution yields.
It is the object of the present invention to provide a method of improving the elution yield of a radioisotope generator, including avoidance of fluctuations in these elution yields, as defined in the opening paragraph, and still yielding an eluate with a high purity. This object can be achieved according to the present invention, in that during elution of the generator air is supplied to the eluent reservoir, which air has a minimized alcohol content. Surprisingly it has been found, that the presence of even small traces of alcohol, such as propanol or ethanol, can dramatically influence the elution yield. Alcohol, in particular propanol, may be employed during assemblage of the generator and is usually employed in a clinic or clinical laboratory for cleaning and sterilizing purposes. It therefore stands to reason, that the air, to which the radioisotope generator is exposed, nearly always comprises traces of alcohol. Upon use of the generator, as described above, this alcohol-contaminated air enters the eluent reservoir and consequently the generator. Apparently these small traces of alcohol are sufficient to derange the elution, resulting in a low and/or fluctuating elution yield.
It will be clear from the above, that the method is in particular applicable to a Mo99-Tc99m generator, i.e. a radioisotope generator of which the column contains a carrier material which at least substantially consists of alumina, wherein the parent isotope is molybdenum-99, wherein the daughter isotope is technetium-99m, and wherein the eluent is a saline solution, preferably a physiological saline solution. It has been observed, that by using the method of the present invention, a high and constant elution yield is guaranteed during the whole elution period, even when unmodified alumina is used as a carrier for the parent isotope molybdenum-99.
The extent to which the alcohol content in the air to be supplied to the eluent reservoir should be reduced depends on the frequency of use of the generator and consequently on the quantity of supplied air per time unit. Preferably the alcohol content of the air to be supplied should be reduced to such an extent, that the alcohol concentration in the eluent never can reach a value of 0.1^1/ml, preferably of 0.05 /.I/ml. This will be demonstrated in a model example attached.
In practice, the alcohol content of the air to be supplied to the eluent reservoir can easily be reduced by using a suitable filter means. A suitable filter means for this purpose is an active-carbon filter, either in the form of active-carbon granules contained in a filter housing, or in the form of an active-carbon filter plate framed in a holder.
The present invention also relates to a radioisotope generator as defined hereinbefore, said generator being characterized in that it comprises filter means suitable for reducing the alcohol content of the air to be supplied to the eluent reservoir during elution of the generator. A suitable filter means comprises an active carbon filter, as stated above. The filter means is preferably sealingly connected to the inlet opening of the eluent reservoir to avoid any inward leakage of alcohol-contaminated air during elution. Normally the inlet opening of the eluent reservoir is equally provided with a bacteria filter to keep the generator in a sterile condition. In a favourable embodiment, the filter means to be used according to the invention is connected between the eluent reservoir and the bacteria filter.
The invention will now be described in greater detail with reference to the following specific examples. EXAMPLE 1
Model experiments with respect to the elution yield relative to the propanol content of the eluent.
The influence of propanol in the eluent (0.9 % aqueous NaCl- solution) on the elution yield is determined, both in a Mo99- Tc99m generator with an unmodified A1203-packed column, and in the same generator with a hydr.-Mn02 modified A1203- packed column. The experiments are performed by dissolving the indicated quantity of propanol into the eluent and by then using said ■■alcohol-contaminated" eluent for eluting the generator. The results of the first five elutions (El.l to El.5) are recorded in Table A below.
EXAMPLE II
Influence of propanol, introduced under the elution cover of a radioisotope generator, on the elution yield
Propanol, in an amount of 0.5 ml, is introduced under the elution cover of a radioisotope generator, so in the proximity of the inlet opening of the eluent reservoir. The Mo99-Tc99m generator used has been provided with an unmodified Al 03-packed column. After the second elution another 0.5 ml quantity of propanol is introduced under the elution cover of the generator. The results of the next elution are recorded in Table B below, both in the absence and in the presence of an active-carbon filter.
Table B
FIGURES
In the accompanying figures suitable embodiments of filter holders, which can be used in the radioisotope of the invention, are shown, both in longitudinal sectional view. The holder shown in Fig. 1 is adapted to accommodate active- carbon granules. This holder comprises a filter housing 10, to the upper edge of which a cover 11 has been clamped, both parts being manufactured from a synthetic material. At the side opposite the cover, the housing is provided with a means for a sealing connection to the inlet opening of the eluent reservoir of a radioisotope generator. This connection means is formed as a luer lock cone 12 and is integrated with the housing of the holder. The cover can be removed from the housing to allow the holder to be filled with active-carbon granules. Upon use in a generator, the air to be supplied to the eluent reservoir is admitted to the holder through the bores 13, recessed in the cover, passes the active-carbon granules and leaves the housing through a bore 14, provided in the bottom thereof. The holder further comprises a centring skirt 15 and strengthening ribs 16. The holder 20 shown in Fig. 2 is adapted to accommodate an active-carbon filter plate to be clamped within the holder between the upper (21) and lower (22) edges thereof.

Claims

1. A method of improving the elution yield of a radioisotope generator, comprising a column containing carrier material adapted to adsorb a parent isotope, said column including an inlet opening and an outlet opening, said outlet opening being connected via an eluate conduit to a tapping point, where a liquid eluate containing a daughter radioisotope can be obtained, said inlet opening being connected via an eluent conduit to an eluent reservoir, said reservoir being provided with an inlet opening for air suppletion to the generator during elution thereof, said method being characterized, in that during elution of the generator air is supplied to the eluent reservoir, which air has a minimized alcohol content.
2. A method as claimed in claim 1, wherein the column of the radioisotope generator contains a carrier material which at least substantially consists of alumina, wherein the parent isotope is molybdenum-99, wherein the daughter isotope is technetium-99m, and wherein the eluent is a saline solution, preferably a physiological saline solution.
3. A method as claimed in claim 1 or 2, characterized in that during elution of the generator air is supplied to the eluent reservoir, the alcohol content of which is reduced to such an extent, that the alcohol concentration in the eluent never can reach a value of 0.1 cl/ml, preferably of 0.05 μ-1/ml.
4. A method as claimed in claim 3, characterized in that the alcohol content in the air to be supplied to the eluent reservoir is reduced by using a suitable filter means.
5. A method as claimed in claim 4, characterized in that the alcohol content in the air to be supplied to the eluent reservoir is reduced by using an active-carbon filter.
6. A radioisotope generator, comprising a column containing carrier material adapted to adsorb a parent isotope, said column including an inlet opening and an outlet opening, said outlet opening being connected via an eluate conduit to a tapping point, where a liquid eluate containing a daughter radioisotope can be obtained, said inlet opening being connected via an eluent conduit to an eluent reservoir, said reservoir being provided with an inlet opening for air suppletion to the generator during elution thereof, said generator being characterized in that it comprises filter means suitable for reducing the alcohol content of the air to be supplied to the eluent reservoir during elution of the generator.
7. A generator as claimed in claim 6, characterized in that the filter means comprises an active-carbon filter.
8. A generator as claimed in claim 6 or 7, characterized in that the filter means is sealingly connected to the inlet opening of the eluent reservoir.
9. A generator as claimed in claim 8, characterized in that the filter means is connected between the eluent reservoir and a bacteria filter, equally sealingly connected to the inlet opening of the eluent reservoir.
EP19920908946 1991-03-14 1992-03-13 Method of improving the elution yield of a radioisotope generator Withdrawn EP0575531A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP19920908946 EP0575531A1 (en) 1991-03-14 1992-03-13 Method of improving the elution yield of a radioisotope generator

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
EP91200555 1991-03-14
EP91200555 1991-03-14
EP19920908946 EP0575531A1 (en) 1991-03-14 1992-03-13 Method of improving the elution yield of a radioisotope generator

Publications (1)

Publication Number Publication Date
EP0575531A1 true EP0575531A1 (en) 1993-12-29

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Country Status (5)

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EP (1) EP0575531A1 (en)
JP (1) JPH07505707A (en)
AU (1) AU1664492A (en)
CA (1) CA2104386A1 (en)
WO (1) WO1992016949A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012089801A2 (en) 2010-12-29 2012-07-05 Holger Blum Process for aerobic cleaning of wastewater
CN113351017A (en) * 2021-06-23 2021-09-07 中国核动力研究设计院 Extraction device for gaseous iodine in loop for producing iodine-125

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11286172B2 (en) 2017-02-24 2022-03-29 BWXT Isotope Technology Group, Inc. Metal-molybdate and method for making the same

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL165872C (en) * 1973-02-20 1981-05-15 Byk Mallinckrodt Cil Bv ISOTOPE GENERATOR FOR THE PRODUCTION OF LIQUIDS CONTAINING 99M TC.
NL7902342A (en) * 1979-03-26 1980-09-30 Byk Mallinckrodt Cil Bv ISOTOPE GENERATOR.
US4472299A (en) * 1981-04-24 1984-09-18 Amersham International Plc Generator for radionuclide and process of use thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9216949A1 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012089801A2 (en) 2010-12-29 2012-07-05 Holger Blum Process for aerobic cleaning of wastewater
DE102010061613A1 (en) 2010-12-29 2012-07-05 Holger Blum Process for the aerobic purification of wastewater
CN113351017A (en) * 2021-06-23 2021-09-07 中国核动力研究设计院 Extraction device for gaseous iodine in loop for producing iodine-125
CN113351017B (en) * 2021-06-23 2022-04-08 中国核动力研究设计院 Extraction device for gaseous iodine in loop for producing iodine-125

Also Published As

Publication number Publication date
JPH07505707A (en) 1995-06-22
WO1992016949A1 (en) 1992-10-01
AU1664492A (en) 1992-10-21
CA2104386A1 (en) 1992-10-01

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