DE2606561A1 - METHOD OF MANUFACTURING A TECHNETIUM-99M LABELED BONE DIAGNOSTIC - Google Patents
METHOD OF MANUFACTURING A TECHNETIUM-99M LABELED BONE DIAGNOSTICInfo
- Publication number
- DE2606561A1 DE2606561A1 DE19762606561 DE2606561A DE2606561A1 DE 2606561 A1 DE2606561 A1 DE 2606561A1 DE 19762606561 DE19762606561 DE 19762606561 DE 2606561 A DE2606561 A DE 2606561A DE 2606561 A1 DE2606561 A1 DE 2606561A1
- Authority
- DE
- Germany
- Prior art keywords
- tin
- technetium
- torr
- solution
- pyrophosphate
- 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.)
- Granted
Links
Classifications
-
- 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
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0474—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group
- A61K51/0478—Organic compounds complexes or complex-forming compounds, i.e. wherein a radioactive metal (e.g. 111In3+) is complexed or chelated by, e.g. a N2S2, N3S, NS3, N4 chelating group complexes from non-cyclic ligands, e.g. EDTA, MAG3
-
- 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
- A61K51/02—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by the carrier, i.e. characterised by the agent or material covalently linked or complexing the radioactive nucleus
- A61K51/04—Organic compounds
- A61K51/0489—Phosphates or phosphonates, e.g. bone-seeking phosphonates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2123/00—Preparations for testing in vivo
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Animal Behavior & Ethology (AREA)
- Physics & Mathematics (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Description
HOECHST AKTIENGESELLSCHAFT 2606561HOECHST AKTIENGESELLSCHAFT 2606561
Aktenzeichen: HOE 76/F 026File number: HOE 76 / F 026
Datum: 18. Februar 1976 Dr.Km/hkaDate: February 18, 1976 Dr.Km/hka
Verfahren zur Herstellung eines Technetium-99m-markierten Knochendiagnostikums Process for the production of a technetium-99m-labeled bone diagnostic
Technetium-99m wird auf Grund seiner kurzen Halbwertszeit und seiner für nuklearmedizinische Untersuchungen günstigen Strahlungseigenschaften in zunehmendem Masse für diagnostische Zwecke eingesetzt. Es wird zur Vermeidung von Transport- und Lagerverlusten vorzugsweise aus dem entsprechenden Nuklidgenerator gewonnen (z.B. entsprechend DOS 2,236,565).Technetium-99m is due to its short half-life and its radiation properties, which are favorable for nuclear medicine examinations increasingly used for diagnostic purposes. It is used to avoid transportation and Storage losses preferably from the corresponding nuclide generator obtained (e.g. according to DOS 2,236,565).
Im Eluat des Technetiura-99m-Generators liegt das Technetium-99m als Pertechnetat in physiologischer Kochsalzlösung vor. In dieser chemischen Form kann es zur Hirn- und Schilddrüsenszintigraphie sowie zur Untersuchung von Kreislaufparametex-n eingesetzt werden. Zur Untersuchung anderer Organe müssen organspezifische Vehikelsubstanzen mit Technetium-99m markiert werden, so z.B. Partikel verschiedener Grosse für die Leber- und Lungendiagnostik, Pyrophosphat oder Diphosphonate für die Skelettdarstellung oder Komplexverbindungen zur Nierenszint igr aph ie.Technetium-99m is in the eluate of the Technetiura-99m generator as pertechnetate in physiological saline solution. In this chemical form it can be used for brain and thyroid scintigraphy as well as for the investigation of circulatory parameters can be used. To examine other organs you need organ-specific vehicle substances labeled with technetium-99m e.g. particles of various sizes for liver and lung diagnostics, pyrophosphate or diphosphonates for the skeleton representation or complex connections to the kidney scint igr aph ie.
7Q9835/00667Q9835 / 0066
Eine Technetium-99m-Markierung beruht darauf, zunächst das Pertechnetat zu reduzieren, um es dann mit der Yehikelsubstanz reagieren zu lassen. Als Reduktionsmittel werden Zinn-(II)-Salze verwendet. Sie reduzieren das Pertechnetat im neutralen Medium. Eine Markierungseinheit besteht z.B. äüs einem mit einem durchstechbaren Stopfen verschlossenen Fläschchen, in dem sich die organspezifische Vehikelsubstanz nebst dem Zinn-(II)-Salz befindet. Da Zinn-(II)-Salze empfindlich gegen Oxidation sind, wird die Lösung lyophilisiert und der Flascheninhalt durch ein inertes Gas, z.B. Stickstoff, geschützt. In dieser Form ist der Inhalt'längere Zeit haltbar. Zur Zubereitung des Diagnostikums, das in gelöster Form meist nur kurze Zeit haltbar ist, wird das Eluat einem Technetium-99m-Generators mittels einer Injektionsspritze in das Fläschchen gefüllt. A technetium-99m mark is based on the To reduce pertechnetate in order to then let it react with the Yehicle substance. Tin (II) salts are used as reducing agents used. They reduce the pertechnetate in the neutral medium. A marking unit consists e.g. of one vial closed with a pierceable stopper, in which the organ-specific vehicle substance and the Tin (II) salt is located. Since tin (II) salts are sensitive to oxidation, the solution is lyophilized and the contents of the bottle protected by an inert gas, e.g. nitrogen. In this form the content can be kept for a longer period of time. For preparation of the diagnostic agent, which is usually only brief in dissolved form Time is stable, the eluate is a technetium-99m generator filled into the vial using an injection syringe.
Zur Knochenszintigraphie sind Technetium-99m-markierte Pyro- und Polyphosphate sowie Diphosphonate geeignet (G. Subramanian und J.G.McAffee, Radiology, 99, S. 192 bis 196; USP 3,735,001; DOS 2,327,870; DOS 2,344,802; DOS 2,424,496; DOS 2,424,453). Sie können in den oben beschriebenen Markierungseinheiten verwendet werden. Es konnte aber, besonders nach längerer Lagerung der Markierungseinheit, in Tier- und Humanversuchen beobachtet werden, dass die unerwünschte Anreicherung von Technetium-99m in der Lebe*· und vor allem in der Milz merklich anstieg. Das bedeutet eine merkliche Qualitätsminderung des Präparates, da zum einen die erwähnten Organe tinnötigerweise durch Strahlen belastet und zum anderen die diagnostische Aussagekraft bei Skeletterkrankungen im allgemeinen und in der Nähe von Leber und Milz im besonderen vermindert ist.Technetium-99m-marked pyro- and polyphosphates and diphosphonates are suitable (G. Subramanian and J.G. McAffee, Radiology, 99, pp. 192 to 196; USP 3,735,001; DOS 2,327,870; DOS 2,344,802; DOS 2,424,496; DOS 2,424,453). They can be used in the marking units described above. But it could, especially after a long time Storage of the marking unit, observed in animal and human experiments, that the undesired accumulation of Technetium-99m in the life * and especially in the spleen rise. This means a noticeable reduction in the quality of the preparation, since, on the one hand, the organs mentioned are deadly burdened by radiation and, on the other hand, the diagnostic value of skeletal diseases in general and in especially in the vicinity of the liver and spleen.
Aufgabe der vorliegenden Erfindung ist es, die obigen Nachteile zu vermeiden und die Lagerfähigkeit der Zinn-(II)-Pyrophosphat-Mischung zu verbessern.The object of the present invention is to avoid the above disadvantages and the shelf life of the tin (II) pyrophosphate mixture to improve.
709835/006$$ 709835/006
606561606561
Das neue Verfahren zur Herstellung einer Markierungseinheit aus Zinn-<II)-Salz und Pyrophosphat zwecks Markierung mit dem Eluat eines Technetium-99m-Generators ist dadurch gekennzeichnet, dass man 0,7 bis 1,3 Gewichtsteile Zinn-(II)-Chlorid und 4,8 bis 9,5 Gewichtsteile Natriusipyrophosphat in 500 tls 2000 Gewichtsteilen Wasser löst, die Lösung auf einen pH-Wert zwischen 3 und 9 einstellt, einfriert und anschliessend das Wasser unter Schmelzen bei einem Wasserdampfpartialdruck von 1 bis 5 Torr, vorzugsweise 2 bis 4 Torr, abzieht und denThe new process for the production of a marking unit from tin (II) salt and pyrophosphate for the purpose of marking with the eluate of a technetium-99m generator is characterized by that 0.7 to 1.3 parts by weight of tin (II) chloride and 4.8 to 9.5 parts by weight of sodium pyrophosphate in 500 tls Dissolves 2000 parts by weight of water, adjusts the solution to a pH value between 3 and 9, freezes and then the Water with melting at a water vapor partial pressure of 1 to 5 Torr, preferably 2 to 4 Torr, withdraws and the
2 —3
Rückstand bei 1O"" bis 10 Torr trocknet.2-3
The residue dries at 10 "" to 10 torr.
Dabei ist es vorteilhaft, die Zinn-(II)-Pyrophosphatlösung mit an der Oberfläche gereinigtem Zinn, zweckmässig in Gestalt von Zinn-Granula zu behandeln. Dadurch werden geringe Anteile von Zinn-( IV)-SaIz reduziert. Vierwertiges Zinn bildet wahrscheinlich zusammen mit zweiwertigem gemischte Hydroxid-Mikropartikel, die ebenfalls mit Technetium-99m markierbar sind, und die bekanntermassen in Leber, Milz und Knochenmark angereichert werden. Das nach dem Trocknen erhaltene Produkt wird steril unter einem inerten Gas, z.B. Stickstoff, in Gefässe, z.B. Rollrandfläschcheii, gefüllt und verschlossen.It is advantageous to use the tin (II) pyrophosphate solution with the tin cleaned on the surface, expediently in shape of tin granules to treat. This reduces small amounts of tin (IV) salt. Forms tetravalent tin probably together with bivalent mixed hydroxide microparticles, which can also be marked with technetium-99m and which are known to be accumulated in the liver, spleen and bone marrow. The one obtained after drying The product is sterile under an inert gas, e.g. nitrogen, in vessels, e.g. crimp neck vials, filled and sealed.
Die so hergestellte Markierungseinheit ist gut lagerfähig. Zur Herstellung des Knochendiagnostikums wird kurz vor der Verwendung das Eluat eines Technetitim-99m-Generators unter sterilen Bedingungen zugegeben. Das so erhaltene Knochendiagnostikum erlaubt auch nach längerer Lagerung der Markierungseinheit eine deutliche Darstellung der Knochen ohne wesentliche Strahlenbelastung anderer Organe.The marking unit produced in this way can be stored well. For the production of the bone diagnostic, shortly before the Use of the eluate from a technetite 99m generator added under sterile conditions. The bone diagnostic agent thus obtained allows the bones to be clearly displayed even after the marking unit has been stored for a long time without significant radiation exposure to other organs.
709835/0066709835/0066
18 g Na4PgO 7 . 10 H2O werden in 1500 ml sterilem bidestillierten Wasser gelöst, Es werden 1,8 g SnCl2 . 2 H2O zugegeben und die Lösung mit 1 η HCi auf einen pH-Wert zwischen 6 und 7 eingestellt. Danach wird die Lösung etwa 20 Minuten lang über einigen oberflächlich gereinigten Zinn-Granula gerührt. Die Lösung wird über ein 0,2 »um Membranfilter steril filtriert, in 1 ml-Portionen in 12 ml Rollrandfläschchen gefüllt und in flüssigem Stickstoff eingefroren. Dann wird der Lösung unter Schmelzen bei 2 bis 5 Torr das Wasser entzogen18 g Na 4 PgO 7 . 10 H 2 O are dissolved in 1500 ml of sterile double-distilled water. 1.8 g of SnCl 2 are added . 2 H 2 O are added and the solution is adjusted to a pH between 6 and 7 with 1 η HCl. The solution is then stirred for about 20 minutes over a few surface-cleaned tin granules. The solution is sterile filtered through a 0.2 µm membrane filter, filled in 1 ml portions into 12 ml crimp-top vials and frozen in liquid nitrogen. The water is then removed from the solution while melting at 2 to 5 torr
—2 3
und der Rückstand bei 10 bis 1O~ Torr nachgetrocknet. Die
Fläschchen werden mit sterilem Stickstoff gefüllt und unter sterilen Bedingungen verschlossen.—2 3
and the residue was dried at 10 to 10 ~ Torr. The vials are filled with sterile nitrogen and sealed under sterile conditions.
Zur Herstellung des Knochendiagnostikums werden 1 bis 10 ml Technetium-SiBm-Pertechnetatlösung, zweckmässig in 0,9%iger NaCl-Lösung als Eluat eines Technetium-99m-Generators mittels Injektionsspritze in das Rollrandfläschchen gegeben.For the preparation of the bone diagnostic, 1 to 10 ml technetium-SiBm-pertechnetate solution, expediently in 0.9% strength NaCl solution as eluate of a technetium-99m generator using Injection syringe placed in the crimp neck vial.
709835/0066709835/0066
Claims (4)
Priority Applications (11)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19762606561 DE2606561C3 (en) | 1976-02-19 | 1976-02-19 | Process for the production of a technetium-99m-labeled bone diagnostic |
NL7701532A NL7701532A (en) | 1976-02-19 | 1977-02-14 | PROCEDURE FOR PREPARING A TECHNETIUM-99M MARKED BONE DIAGNOSTIC. |
CH190777A CH626253A5 (en) | 1976-02-19 | 1977-02-16 | Process for the production of a labelling unit |
IT2041677A IT1074322B (en) | 1976-02-19 | 1977-02-17 | PORCESS FOR THE PREPARATION OF A BONE DIAGNOSTIC MEDIA MARKED WITH TECNEZIO / 99M |
LU76794A LU76794A1 (en) | 1976-02-19 | 1977-02-17 | |
GB695877A GB1565865A (en) | 1976-02-19 | 1977-02-18 | Process for the manufacture of a technetium-997 labelled diagnostic agent for bone scanning |
DK71277A DK71277A (en) | 1976-02-19 | 1977-02-18 | PROCEDURE FOR THE MANUFACTURE OF A MARKING UNIT AND ITS USE FOR THE MANUFACTURE OF A BONE DIAGNOSTIC |
IE35077A IE44699B1 (en) | 1976-02-19 | 1977-02-18 | Process for the manufacture of a technetium-99m labelled diagnostic agent for bone scanning |
AT111077A AT357271B (en) | 1976-02-19 | 1977-02-18 | METHOD FOR IMPROVING THE STORAGE STABILITY OF A TIN (II) -PYROPHOSPHATE MIXTURE |
BE175111A BE851656A (en) | 1976-02-19 | 1977-02-21 | PROCESS FOR PREPARING A MARKED DIAGNOSIS AGENT WITH TECHNETIUM -99M |
FR7704935A FR2341306A1 (en) | 1976-02-19 | 1977-02-21 | PROCESS FOR PREPARING A MARKED DIAGNOSIS AGENT WITH TECHNETIUM-99M, USED IN PARTICULAR FOR THE EXAMINATION OF BONES AND PRODUCT OBTAINED |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19762606561 DE2606561C3 (en) | 1976-02-19 | 1976-02-19 | Process for the production of a technetium-99m-labeled bone diagnostic |
Publications (3)
Publication Number | Publication Date |
---|---|
DE2606561A1 true DE2606561A1 (en) | 1977-09-01 |
DE2606561B2 DE2606561B2 (en) | 1980-05-14 |
DE2606561C3 DE2606561C3 (en) | 1981-02-05 |
Family
ID=5970237
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE19762606561 Expired DE2606561C3 (en) | 1976-02-19 | 1976-02-19 | Process for the production of a technetium-99m-labeled bone diagnostic |
Country Status (11)
Country | Link |
---|---|
AT (1) | AT357271B (en) |
BE (1) | BE851656A (en) |
CH (1) | CH626253A5 (en) |
DE (1) | DE2606561C3 (en) |
DK (1) | DK71277A (en) |
FR (1) | FR2341306A1 (en) |
GB (1) | GB1565865A (en) |
IE (1) | IE44699B1 (en) |
IT (1) | IT1074322B (en) |
LU (1) | LU76794A1 (en) |
NL (1) | NL7701532A (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2020258282B2 (en) * | 2019-04-18 | 2023-01-19 | Colgate-Palmolive Company | Improved methods for synthesizing stannous pyrophosphate |
-
1976
- 1976-02-19 DE DE19762606561 patent/DE2606561C3/en not_active Expired
-
1977
- 1977-02-14 NL NL7701532A patent/NL7701532A/en not_active Application Discontinuation
- 1977-02-16 CH CH190777A patent/CH626253A5/en not_active IP Right Cessation
- 1977-02-17 LU LU76794A patent/LU76794A1/xx unknown
- 1977-02-17 IT IT2041677A patent/IT1074322B/en active
- 1977-02-18 DK DK71277A patent/DK71277A/en unknown
- 1977-02-18 GB GB695877A patent/GB1565865A/en not_active Expired
- 1977-02-18 AT AT111077A patent/AT357271B/en not_active IP Right Cessation
- 1977-02-18 IE IE35077A patent/IE44699B1/en unknown
- 1977-02-21 FR FR7704935A patent/FR2341306A1/en active Granted
- 1977-02-21 BE BE175111A patent/BE851656A/en not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
CH626253A5 (en) | 1981-11-13 |
ATA111077A (en) | 1979-11-15 |
IT1074322B (en) | 1985-04-20 |
IE44699B1 (en) | 1982-02-24 |
LU76794A1 (en) | 1977-09-12 |
BE851656A (en) | 1977-08-22 |
DE2606561B2 (en) | 1980-05-14 |
AT357271B (en) | 1980-06-25 |
IE44699L (en) | 1977-08-19 |
DK71277A (en) | 1977-08-20 |
GB1565865A (en) | 1980-04-23 |
NL7701532A (en) | 1977-08-23 |
FR2341306B1 (en) | 1980-02-01 |
FR2341306A1 (en) | 1977-09-16 |
DE2606561C3 (en) | 1981-02-05 |
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Legal Events
Date | Code | Title | Description |
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C3 | Grant after two publication steps (3rd publication) | ||
8339 | Ceased/non-payment of the annual fee |