Method for synthesizing labelled compounds

• US 6,172,207 B1
• Filed: 07/29/1998
• Issued: 01/09/2001
• Est. Priority Date: 05/02/1996
• Status: Expired due to Term

• Current Assignee: GE Medical Systems Benelux (General Electric Company), Université de Liège
• Original Assignee: Coincidence S. A., Université de Liège, Universite libre de Bruxelles
• Inventors: Monclus, Michel, Van Namen, John J., Damhaut, Philippe E., Lemaire, Christian F., Morelle, Jean-Luc E., Lauricella, Benjamin P., Mulleneers, Eric, Luxen, Andre
• Primary Examiner(s): Wilson, James O.
• Application Number:
  US08/981,331
• Time in Patent Office: 895 Days
• Field of Search: 536/18.4, 536/18.5, 536/122, 536/124, 424/1.1, 422/102, 422/103, 422/104, 422/159
• US Class Current: 536/18.4
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/005 Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids
• CPC Class Codes: C07H 5/02 to halogen

Abstract

A process and a device for synthesizing labeled compounds. The process involves preparing a labeling agent, labeling a precursor with the labeling agent, where the precursor is a protected substrate, and deprotecting the labeled precursor to convert the labeled precursor to a labeled compound by passing the labeled precursor through a solid support in a column or a cartridge. The process may be used to convert labeled tetraacetylfluoroglucose (TAFg) to labeled fluoro-deoxy-glucose (FDG) for use in nuclear medical imaging. The process is more rapid than conventional methods and is performed at room temperature rather than high temperature for conventional technology.

Claims

1. A process for synthesizing labeled compounds with an isotopic element, comprising the steps of:

preparing a labelling agent;

labelling a precursor with the labelling agent, wherein the precursor is a protected substrate;

pre-purifying the labelled precursor;

retaining the labelled precursor on a solid support;

deprotecting the labelled precursor, wherein deprotecting the labelled precursor converts the labelled precursor into a labelled compound in a deprotection step, wherein the labelled compound is free of the solid support; and

formulating a final solution,

wherein the deprotection step is performed directly on the solid support which is contained in a column or cartridge and wherein the labelled compound is 2-[¹⁸F]fluoro-2-deoxy-D-glucose (FGD).

2. The process according to claim 1, wherein the column or cartridge is of a commercial type.

3. The process according to claim 1, wherein the deprotection step is performed directly in the solid support column or cartridge being used for pre-purification.

4. The process according to claim 1, wherein the solid support is of a normal, reverse or intermediate polarity phase type.

5. The process according to claim 1, wherein the solid support is of a low polarity.

6. The process according to claim 1, wherein the deprotection step is performed on a solid support of an ion exchange phase type or of a mixture of ion exchange phase type with one or several normal or reverse phases.

7. The process according to claim 1, wherein the deprotection step is performed on a column or cartridge selected from the group consisting of C18, C8, tC18, NH2, diol, and polystyrene divinylbenzene (SDB).

8. The process according to claim 1, wherein the cartridge or column contains between 50 mg and 10 g of a solid support.

9. The process according to claim 1, wherein the solid support is in the form of grains, membranes, sheets or capillaries.

10. The process according to claim 1, wherein, during the deprotection step, the solid support is impregnated with an agent enabling or increasing said deprotection.

11. The process according to claim 1, wherein the deprotection is performed by saponification.

12. The process according to claim 11, wherein said saponification is carried out with the help of an NaOH aqueous solution.

13. The process according to claim 1, wherein said deprotection is carried out by an acid hydrolysis.

14. The process according to claim 13, wherein said hydrolysis is carried out with an HCl aqueous solution.

15. The process according to claim 1, wherein the solid support contained in the column or cartridge during the deprotection step remains in acid or alkaline media for 1 to 5 minutes.

16. The process according to claim 15, wherein base or acid concentrations between 0.2 and 2M are used.

17. The process according to claim 1, wherein the deprotection agent is the solid support itself.

18. The process according to claim 1, wherein, after the deprotection step, the cartridge or column is eluted by an eluent selected from the group consisting of water, an aqueous solution, and a physiological solution, wherein said eluent drains the labelled compound with the solution and wherein the labelled compound is collected.

19. The process according to claim 1, wherein a solution of labelled precursor in acetonitrile is used and wherein said solution is diluted 5:

1 with water or an aqueous solution.

20. The process according to claim 1, wherein the protected precursor is 1,3,4,6-tetra-O-acetyl-2-trifluoromethanesulphonyl-β

-D-mannosepyranose (TAFg).

21. The process according to claim 8, wherein the cartridge or column contains between between 200 mg and 800 mg of a solid support.

22. The process according to claim 18, wherein the collected labelled compound is purified, filtered or sterilized.

23. The process according to claim 2, wherein said column or cartridge is implemented in a Solid Phase Extraction (SPE) technique.