WO2013171198A1 - Satz und verfahren zur herstellung eines radiopharmakons - Google Patents
Satz und verfahren zur herstellung eines radiopharmakons Download PDFInfo
- Publication number
- WO2013171198A1 WO2013171198A1 PCT/EP2013/059909 EP2013059909W WO2013171198A1 WO 2013171198 A1 WO2013171198 A1 WO 2013171198A1 EP 2013059909 W EP2013059909 W EP 2013059909W WO 2013171198 A1 WO2013171198 A1 WO 2013171198A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydrochloric acid
- sentence
- vial
- hcl
- solution
- Prior art date
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
- A61K51/048—DTPA (diethylenetriamine tetraacetic acid)
Definitions
- the invention relates to a kit and a method for producing a radiopharmaceutical.
- PET positron emission spectroscopy
- SPECT single-photon emission computed tomography
- DOTATOC edotreotide
- Radionuclides for example, 68 gallium marked and used as a radiopharmaceutical, also called tracer.
- the radiopharmaceutical binds in the human body to certain receptors that are overexpressed especially in tumor cells.
- the increased beta-plus decay of 68 gallium can be detected and localized.
- the isotope 68 gallium decomposes 89% with a half-life of 67.629 minutes, emitting a positron of 1.9 MeV maximum and 11% electron capture; each in the stable isotope 68 zinc.
- the radiated photons can be detected with appropriate detectors and by reconstruction of several detection events, the location of the annihilation can be determined quite accurately.
- the radiopharmaceutical can not be kept for a long time but must be prepared relatively short time before the intended use. - -
- Gallium is produced from 68 germanium by means of so-called Gallium 68 generators, also called Ge / Ga generators.
- 68 Germanium has one
- hydrochloric acid with a normality of 0.05 N to 0.4 N is used for the elution.
- the elution volume is between 5 ml and 10 ml.
- the eluate is accordingly salt-fast and can not be used directly for labeling peptides.
- the eluate is treated with a large volume of concentrated hydrochloric acid, the 68 Ga by means of a
- the gallium 68 is held on a cation exchanger (SCX) and then with a
- Acetone / hydrochloric acid solution eluted.
- the recovered product therefore contains acetone, that before application to the human body by means of distillation
- the object of the invention is to provide a kit, also called kit, for the improved production of a radiopharmaceutical and a corresponding improved method.
- the object is achieved according to fiction by a sentence with the features of claim 1 and a method having the features of claim 12.
- a kit according to the invention comprises:
- SCX cartridge a sterile cation exchange cartridge
- reaction vial with a label precursor especially a lyophilized label precursor
- a vial can also be called an ampoule or septum bottle.
- the buffer salt can be contained, for example, in the reaction vial or in the solvent vial.
- the content of the reaction vial is preferably lyophilized.
- lyophilized ascorbic acid or another suitable stabilizer may be provided in the reaction vial.
- the stabilizer prevents the - -
- Radiolytic degradation of the labeled substance during use of the radiopharmaceutical is Radiolytic degradation of the labeled substance during use of the radiopharmaceutical.
- a buffer salt for example, ammonium acetate or sodium acetate can be used.
- a 68 Ge / 68 Ga generator provides the 68 gallium needed for the label.
- the 68 Ge / 68 Ga generator is eluted by means of hydrochloric acid, for example the concentration 0, 1 mol / 1. In this way, 68 gallium is eluted.
- the generator eluate is fed to the SCX cartridge.
- a SCX cartridge for example, a silica gel based (silica based) cartridge can be used.
- the SCX cartridge is preconditioned with 1 ml hydrochloric acid
- the resultant in the reaction vial reaction solution may be heated to 90 ° C to 100 ° C optionally for example over a period of 5 minutes to 15 minutes, in particular seven minutes in order to accelerate the reaction, wherein the 68 gallium with the labeling precursor to form of the tracer.
- the reaction can also be carried out at room temperature, whereby correspondingly more time may be necessary.
- the concentration of unbound 68 gallium is preferably less than 5%.
- the radiochemical purity of the tracer is higher than 95%.
- Reaction mixture contains no toxic or questionable substances, so that no subsequent purification is required.
- the radiochemical yield is about 82% (ndc - non-decay corrected - not decay corrected).
- the tracer thus prepared can then be used as a radiopharmaceutical without further purification.
- the set of the invention can be used to routinely available application in clinical practice in 68 Ga-labeling process.
- the kit according to the invention reduces the handling of concentrated hydrochloric acid in the purification and concentration procedure of the 68 Ga eluate.
- the achievable end product (tracer) is available with high purity and in high yield of about 80% to 95%.
- Gas chromatograph is required. In this way, it is possible to produce sets that are relatively easy to apply by adding the solution to the lyophilized mixture of medical personnel without the need for expensive laboratory equipment.
- the tracers obtained are longer stable than tracers known from the prior art, so that multidose preparations can be produced for the labeling and examination of several patients.
- the reaction vial contains a lyophilized mixture of sodium acetate and DTPA
- the tracer thus formed can in particular for - -
- Functional diagnostics of the kidney can be used by positron emission tomography.
- ammonium acetate can be used in principle, but sodium acetate is better suited for lyophilization.
- the reaction vial contains:
- the solution vial contains:
- Solvent from the Abstol and the solution used for the elution of the SCX cartridge solution of the elution vial is between 3 and 4.
- the solution vial contains:
- the elution vial contains 0.25 ml to 3 ml of eluting solution of 5 mol / l sodium chloride and 5.5 mol / l hydrochloric acid with 11 ⁇ to 100 ⁇ , preferably 25 ⁇ 5.5 mol / 1 hydrochloric acid per ml of 5 mol / l sodium chloride.
- a method according to the invention for the production of a radiopharmaceutical comprises the steps:
- the method can be carried out by means of the sentence according to the invention.
- Figure 1 is a schematic view of a sentence for producing a
- Figure 2 shows an arrangement for producing a radiopharmaceutical by means of the sentence.
- FIG. 1 shows a schematic view of a set 1 for the production of a radiopharmaceutical.
- the first sentence includes:
- reaction vial 3 with a mixture comprising a
- the mixture in the reaction vial 3 is lyophilized.
- the mixture in reaction vial 3 optionally comprises ascorbic acid C ö HgO 6 or another radical scavenger.
- the solvent is preferably formed as an aqueous solution of acetic acid C 2 H 4 O 2 and hydrochloric acid HCl.
- the buffer salt ammonium acetate CH 3 COONH 4 or sodium acetate C 2 H 3 Na0 2 is provided.
- the cation exchange cartridge 2 can be preconditioned with hydrochloric acid HCl and water H 2 O, in particular with 1 ml hydrochloric acid HCl of concentration 5.5 mol / l and 10 ml water H 2 0.
- the reaction vial 3 contains:
- the solution vial 4 contains:
- the elution vial 5 contains an amount of 0.25 ml to 3 ml of elution solution of 5 mol / 1 sodium chloride NaCl and 5.5 mol / 1 hydrochloric acid HCl with 11 ⁇ to 100 ⁇ , preferably 25 ⁇ 5.5 mol / 1 hydrochloric acid HCl each ml of 5 mol / l sodium chloride NaCl.
- the kit 1 may additionally comprise a vial with a neutralization buffer, especially a sodium phosphate buffer.
- FIG. 2 shows an arrangement for producing a radiopharmaceutical 8 by means of the sentence 1.
- a 68 Ge / 68 Ga-generator 6 provides the required 68 for marking gallium.
- the 68 Ge / 68 Ga generator 6 is hydrochloric acid HCl, for example, the
- reaction solution resulting in reaction vial 3 can be optionally heated to 90 ° C to 100 ° C, for example, over a period of 5 minutes to 15 minutes, especially seven minutes, to accelerate the reaction in which the 68 gallium with the labeling precursor to Education of the
- Radiopharmaceutical 8 also called tracer
- the reaction can also take place at room temperature, whereby it requires more time accordingly.
- a sterile phosphate buffer can be added. , ,
- the reaction product can optionally be filtered by means of a sterile filter 7.
- the tracer thus prepared can then be used as a radiopharmaceutical 8.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Optics & Photonics (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Description
Claims
Priority Applications (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR112014028607A BR112014028607A2 (pt) | 2012-05-18 | 2013-05-14 | Kit para a produção de um radiofármaco e método para a preparação de um radiofármaco. |
US14/402,038 US20150098895A1 (en) | 2012-05-18 | 2013-05-14 | Set and method for the production of a radiopharmaceutical |
CA2873732A CA2873732A1 (en) | 2012-05-18 | 2013-05-14 | Set and method for the production of a radiopharmaceutical |
EP13722439.0A EP2849806A1 (de) | 2012-05-18 | 2013-05-14 | Satz und verfahren zur herstellung eines radiopharmakons |
AU2013261867A AU2013261867B2 (en) | 2012-05-18 | 2013-05-14 | Set and method for the production of a radiopharmaceutical |
IN10398DEN2014 IN2014DN10398A (de) | 2012-05-18 | 2014-12-05 | |
AU2016222380A AU2016222380B2 (en) | 2012-05-18 | 2016-08-31 | Set and method for the production of a radiopharmaceutical |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE102012208377.4A DE102012208377B4 (de) | 2012-05-18 | 2012-05-18 | Satz und Verfahren zur Herstellung eines Radiopharmakons |
DE102012208377.4 | 2012-05-18 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2013171198A1 true WO2013171198A1 (de) | 2013-11-21 |
Family
ID=48430790
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2013/059909 WO2013171198A1 (de) | 2012-05-18 | 2013-05-14 | Satz und verfahren zur herstellung eines radiopharmakons |
Country Status (8)
Country | Link |
---|---|
US (1) | US20150098895A1 (de) |
EP (1) | EP2849806A1 (de) |
AU (2) | AU2013261867B2 (de) |
BR (1) | BR112014028607A2 (de) |
CA (1) | CA2873732A1 (de) |
DE (1) | DE102012208377B4 (de) |
IN (1) | IN2014DN10398A (de) |
WO (1) | WO2013171198A1 (de) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170125326A (ko) * | 2015-01-30 | 2017-11-14 | 어드밴스드 액셀러레이터 어플리케이션즈 인터내셔널 에스.에이. | 68Ge/68Ga 발생기로부터 유래하는 용출물로부터 Ga-68을 정제하는 방법 및 이러한 방법에 사용하기 위한 크로마토그래피 컬럼 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006056395A2 (de) * | 2004-11-26 | 2006-06-01 | Johannes Gutenberg-Universität Mainz | Verfahren und vorrichtung zur isolierung eines chemisch und radiochemisch gereinigten 68ga-radionuklid und zum markieren eines markierungsvorläufers mit dem 68ga-radionuklid |
WO2009102378A2 (en) * | 2007-12-03 | 2009-08-20 | Ge Healthcare Limited | Purification of 68ge/68ga generator eluate from fe(iii) intended to improve specific radioactivity of 68ga-based radiopharmaceuticals |
WO2011106846A1 (en) * | 2010-03-03 | 2011-09-09 | Australian Nuclear Science And Technology Organisation | Gallium-68 purification |
-
2012
- 2012-05-18 DE DE102012208377.4A patent/DE102012208377B4/de active Active
-
2013
- 2013-05-14 CA CA2873732A patent/CA2873732A1/en not_active Abandoned
- 2013-05-14 EP EP13722439.0A patent/EP2849806A1/de not_active Ceased
- 2013-05-14 BR BR112014028607A patent/BR112014028607A2/pt not_active IP Right Cessation
- 2013-05-14 US US14/402,038 patent/US20150098895A1/en not_active Abandoned
- 2013-05-14 WO PCT/EP2013/059909 patent/WO2013171198A1/de active Application Filing
- 2013-05-14 AU AU2013261867A patent/AU2013261867B2/en not_active Ceased
-
2014
- 2014-12-05 IN IN10398DEN2014 patent/IN2014DN10398A/en unknown
-
2016
- 2016-08-31 AU AU2016222380A patent/AU2016222380B2/en not_active Ceased
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006056395A2 (de) * | 2004-11-26 | 2006-06-01 | Johannes Gutenberg-Universität Mainz | Verfahren und vorrichtung zur isolierung eines chemisch und radiochemisch gereinigten 68ga-radionuklid und zum markieren eines markierungsvorläufers mit dem 68ga-radionuklid |
WO2009102378A2 (en) * | 2007-12-03 | 2009-08-20 | Ge Healthcare Limited | Purification of 68ge/68ga generator eluate from fe(iii) intended to improve specific radioactivity of 68ga-based radiopharmaceuticals |
WO2011106846A1 (en) * | 2010-03-03 | 2011-09-09 | Australian Nuclear Science And Technology Organisation | Gallium-68 purification |
Non-Patent Citations (4)
Title |
---|
DIRK MUELLER ET AL: "Simplified NaCl Based 68 Ga Concentration and Labeling Procedure for Rapid Synthesis of 68 Ga Radiopharmaceuticals in High Radiochemical Purity", BIOCONJUGATE CHEMISTRY, vol. 23, no. 8, 15 August 2012 (2012-08-15), pages 1712 - 1717, XP055071483, ISSN: 1043-1802, DOI: 10.1021/bc300103t * |
I. VELIKYAN: "Synthesis, Characterisation and Application of 68Ga-labelled Macromolecules", DISSERTATION, 2005 |
MICHAEL K. SCHULTZ ET AL: "A new automated NaCl based robust method for routine production of gallium-68 labeled peptides", APPLIED RADIATION AND ISOTOPES, vol. 76, 1 June 2013 (2013-06-01), pages 46 - 54, XP055071485, ISSN: 0969-8043, DOI: 10.1016/j.apradiso.2012.08.011 * |
VELIKYAN IRINA: "Positron emitting [68Ga]Ga-based imaging agents: chemistry and diversity", MEDICINAL CHEMISTRY, BENTHAM SC. PUBL, SHARIQAH (UNITED ARAB EMIRATES), vol. 7, no. 5, 1 September 2011 (2011-09-01), pages 345 - 379, XP008163613, ISSN: 1875-6638, DOI: 10.2174/157340611796799195 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20170125326A (ko) * | 2015-01-30 | 2017-11-14 | 어드밴스드 액셀러레이터 어플리케이션즈 인터내셔널 에스.에이. | 68Ge/68Ga 발생기로부터 유래하는 용출물로부터 Ga-68을 정제하는 방법 및 이러한 방법에 사용하기 위한 크로마토그래피 컬럼 |
KR102490458B1 (ko) * | 2015-01-30 | 2023-01-19 | 어드밴스드 액셀러레이터 어플리케이션즈 인터내셔널 에스.에이. | 68Ge/68Ga 발생기로부터 유래하는 용출물로부터 Ga-68을 정제하는 방법 및 이러한 방법에 사용하기 위한 크로마토그래피 컬럼 |
Also Published As
Publication number | Publication date |
---|---|
CA2873732A1 (en) | 2013-11-21 |
AU2013261867A1 (en) | 2014-11-20 |
AU2016222380B2 (en) | 2017-10-05 |
BR112014028607A2 (pt) | 2017-10-03 |
EP2849806A1 (de) | 2015-03-25 |
US20150098895A1 (en) | 2015-04-09 |
IN2014DN10398A (de) | 2015-08-14 |
DE102012208377B4 (de) | 2015-07-23 |
AU2013261867B2 (en) | 2016-06-02 |
AU2013261867A2 (en) | 2014-12-18 |
AU2016222380A1 (en) | 2016-09-22 |
DE102012208377A1 (de) | 2013-11-21 |
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