CA2345838A1 - Method for the synthesis of radiolabeled compounds - Google Patents

Method for the synthesis of radiolabeled compounds Download PDF

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Publication number
CA2345838A1
CA2345838A1 CA 2345838 CA2345838A CA2345838A1 CA 2345838 A1 CA2345838 A1 CA 2345838A1 CA 2345838 CA2345838 CA 2345838 CA 2345838 A CA2345838 A CA 2345838A CA 2345838 A1 CA2345838 A1 CA 2345838A1
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CA
Canada
Prior art keywords
loop
compound
radiolabeling
precursor chemical
iodomethane
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
Application number
CA 2345838
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French (fr)
Other versions
CA2345838C (en
Inventor
Alan A. Wilson
Armando Garcia
Li Jin
Sylvain Houle
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Centre for Addiction and Mental Health
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Centre for Addiction and Mental Health
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Publication date
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Priority to CA 2345838 priority Critical patent/CA2345838C/en
Publication of CA2345838A1 publication Critical patent/CA2345838A1/en
Application granted granted Critical
Publication of CA2345838C publication Critical patent/CA2345838C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/001—Acyclic or carbocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Steroid Compounds (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

A new method of [11C]-methylation is described which attains the goals of simplicity, high radiochemical yields, speed, versatility, and automation.
A
standard HPLC injection loop on a standard HPLC injection valve is loaded with a solution of precursor in DMF or DMSO (+ base if required). At ambient temperature [11C]-iodomethane is passed through the loop for 3-4 min with >90% trapping of activity. After a further 1-5 min, the contents of the loop are quantitatively injected onto the HPLC column for purification. Radiochemical yields are equal to or superior to conventional solution methods in all cases, even though no heat is applied. [11C]-Labelled radiotracers which have been prepared by this method for human or animal studies include Raclopride, N-methylspiperone, Ro 15-1788, FLB 457, RTI-32, Rolipram, SCH 23390, and SKF 82957. Since no vials, transfer lines, cooling, heating, or sealing valves are required, no transfer losses occur, yields are high, and clean-up is minimal, this "loop method" is ideal for most radiopharmaceuticals prepared from [11C]-iodomethane.

Claims (10)

1. A method for radiolabeling precursor chemical compounds comprising the steps of:
- injecting a sample comprising a precursor chemical compound, dissolved in an appropriate solvent, into an injection loop of a high performance liquid chromatograph (HPLC);
- injecting a radiolabeling reagent into the injection loop until a maximum amount of radioactivity is reached;
- allowing the radiolabeling reagent to react with the precursor chemical compound, to provide a reaction mixture comprising a radiolabeled compound;
- injecting the reaction mixture into the HPLC column; and - isolating the radiolabeled compound.
2. The method according to claim 1, wherein the radiolabeling reagent is a volatile and condensable compound.
3. The method according to claim 2, wherein the radiolabeling reagent is selected from the group consisting of [11C]-ethyl iodide, [11C]-propyl iodide, [11C]-methyliodide and [11C]-acetyl iodide.
4. The method according to claim 3, wherein the radiolabeling reagent is [11C]-methyliodide.
5. The method according to any of claims 1 to 4, wherein the precursor chemical compound is in the form of an acid salt and the sample further comprises a base.
6. The method according to claim 4 or 5, wherein the [11C]-iodomethane is reacted with the precursor chemical compound for about 0.5 to about 20 minutes.
7. The method according to any of claims 1 to 6, wherein the solvent is selected from the group consisting of dimethylformamide and dimethylsulfoxide.
8. The method according to any of claims 1 or 7, wherein the sample further comprises a catalyst.
9. A radiolabeled compound prepared using a method according to any of claims 1 to 8.
10. A [11C]-methylated compound prepared using a method according to claim 4.
CA 2345838 2001-01-31 2001-05-01 Method for the synthesis of radiolabeled compounds Expired - Fee Related CA2345838C (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CA 2345838 CA2345838C (en) 2001-01-31 2001-05-01 Method for the synthesis of radiolabeled compounds

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CA 2345838 CA2345838C (en) 2001-01-31 2001-05-01 Method for the synthesis of radiolabeled compounds
USUNKNOWN 2003-08-05

Publications (2)

Publication Number Publication Date
CA2345838A1 true CA2345838A1 (en) 2002-07-31
CA2345838C CA2345838C (en) 2010-02-02

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Family Applications (1)

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CA 2345838 Expired - Fee Related CA2345838C (en) 2001-01-31 2001-05-01 Method for the synthesis of radiolabeled compounds

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CA (1) CA2345838C (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005003151A2 (en) * 2003-06-25 2005-01-13 Peregrine Pharmaceuticals, Inc. Method and apparatus for continuous large-scale radiolabeling of proteins
CN100471866C (en) * 2003-06-25 2009-03-25 派瑞格恩医药公司 Method and apparatus for continuous large-scale radiolabeling of proteins
US8312780B2 (en) 2010-06-25 2012-11-20 Mettler-Toledo Ag Sampling device and method
US8365617B2 (en) 2010-06-25 2013-02-05 Mettler-Toledo Ag Sampling device
CN110790696A (en) * 2018-08-03 2020-02-14 田海滨 11Preparation method and preparation system of C- α -methyl-L-tryptophan

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005003151A2 (en) * 2003-06-25 2005-01-13 Peregrine Pharmaceuticals, Inc. Method and apparatus for continuous large-scale radiolabeling of proteins
WO2005003151A3 (en) * 2003-06-25 2005-04-07 Peregrine Pharmaceuticals Inc Method and apparatus for continuous large-scale radiolabeling of proteins
EP1964847A3 (en) * 2003-06-25 2008-09-17 Peregrine Pharmaceuticals, Inc. Method and apparatus for continuous large-scale radiolabeling of proteins
CN100471866C (en) * 2003-06-25 2009-03-25 派瑞格恩医药公司 Method and apparatus for continuous large-scale radiolabeling of proteins
US7591953B2 (en) 2003-06-25 2009-09-22 Peregrine Pharmaceuticals, Inc. Methods and apparatus for continuous large-scale radiolabeling of proteins
US8137540B2 (en) 2003-06-25 2012-03-20 Peregrine Pharmaceuticals, Inc. Methods and apparatus for continuous large-scale radiolabeling
US8312780B2 (en) 2010-06-25 2012-11-20 Mettler-Toledo Ag Sampling device and method
US8365617B2 (en) 2010-06-25 2013-02-05 Mettler-Toledo Ag Sampling device
US8789431B2 (en) 2010-06-25 2014-07-29 Mettler-Toledo Ag Sampling device and method of use thereof
CN110790696A (en) * 2018-08-03 2020-02-14 田海滨 11Preparation method and preparation system of C- α -methyl-L-tryptophan

Also Published As

Publication number Publication date
CA2345838C (en) 2010-02-02

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