Solid-phase nucleophilic fluorination

• US 20040236085A1
• Filed: 07/15/2004
• Published: 11/25/2004
• Est. Priority Date: 06/29/2001
• Status: Abandoned Application

• Current Assignee: GE Healthcare Limited (General Electric Company)
• Original Assignee: GE Healthcare Limited (General Electric Company)
• Inventors: Luthra, Sajinder Kaur, Wadsworth, Harry John, Brady, Frank, Glaser, Matthias Eberhard, Gibson, Alexander Mark
• Application Number:
  US10/482,540
• Publication Number:
  US 20040236085A1
• Time in Patent Office: Days
• US Class Current: 536/1.11
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07B 59/00 Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
• CPC Class Codes: C07C 25/13 containing fluorine
• CPC Class Codes: C07C 255/42 the carbon skeleton being further substituted by singly-bound nitrogen atoms, not being further bound to other hetero atoms
• CPC Class Codes: C07C 309/65 of a saturated carbon skeleton
• CPC Class Codes: C07H 5/02 to halogen

Abstract

The present invention relates to novel solid-phase processes for the production of radiolabelled tracers, in particular for the production of ¹⁸F-labelled compounds which may be suitable for use as Positron Emission Tomography (PET) radiotracers. The invention also comprises radiopharmaceutical kits using these novel processes.

Claims

1. A process for the production of an ¹⁸F-labelled tracer which comprises treatment of a resin-bound precursor of formula (I)

SOLID SUPPORT-LINKER-X-TRACER 

 

(I)

wherein X is a group which promotes nucleophilic substitution at a specific site on the attached TRACER;

with ¹⁸F⁻

to produce the labelled tracer of formula (II)

¹⁸F-TRACER 

 

(II).

2. A process for the production of an ¹⁸F-labelled tracer according to claim 1 which comprises treatment of a resin-bound precursor of formula (Ia)

SOLID SUPPORT-LINKER-SO₂— O—

TRACER 

 

(Ia)

with ¹⁸F⁻

to produce the labelled tracer of formula (II)

¹⁸F-TRACER 

 

(II)

followed by optionally

(i) removal of excess ¹⁸F⁻

, for example by ion-exchange chromatography; and

/or

(ii) removal of any protecting groups; and

/or

(iii) removal of organic solvent; and

/or

(iv) formulation of the resultant compound of formula (II) as an aqueous solution.

3. A process according to claim 1 for the production of 2-¹⁸F-fluoro-2-deoxy-D-glucose (¹⁸F-FDG) which comprises treatment of a solid support-bound precursor of formula (Ib):

4. A process according to claim 1 for the production of 3′

-deoxy-3′

-¹⁸F-fluorothymidine (¹⁸F-FLT) which comprises treatment of a solid support-bound precursor of formula (Ic);

5. A process according to claim 1 for the production of 2-(1,1-dicyanopropen-2-yl)-6-(2-fluoroethyl)-methylamino)-naphthalene (FDDNP) which comprises treatment of a solid support bound precursor of formula (Ih):

6. A process according to claim 1 for the production of an ¹⁸F-labelled tracer which comprises treatment of a solid support-bound precursor of formula (Id)

7. A process according to claim 1 for the production of 6-L-¹⁸F-fluorodopa (¹⁸F-FDOPA) which comprises treatment of a solid support-bound precursor of formula (Ie):

8. A process for the manufacture of a ¹⁸F-labelled tracer of formula (II), according to any one of claim 1, for use in PET.

13. A radiopharmaceutical kit for the preparation of an ¹⁸F-labelled tracer for use in PET, which comprises:

(i) a vessel containing a compound of formula (I), as defined in claim 1;

and

(ii) means for eluting the vessel with a source of ¹⁸F⁻

;

(iii) an ion-exchange cartridge for removal of excess ¹⁸F⁻

; and

optionally

(iv) a cartridge for solid-phase deprotection of the resultant product of formula (II), as defined in claim 1.

14. A cartridge for a radiopharmaceutical kit for the preparation of an ¹⁸F-labelled tracer for use in PET which comprises:

(i) a vessel containing a compound of formula (I) as defined in claim 1;

and

(ii) means for eluting the vessel with a source of ¹⁸ F⁻

.

15. A method for obtaining a diagnostic PET image which comprises the step of using a radiopharmaceutical kit according to claim 13.

9. A compound of formula (Ib)

10. A compound of formula (Ic):

11. A compound of formula (Ih):

12. A compound of formula (Ie):