Synthesizing pet tracers using [F-18]sulfonyl fluoride as a source of [F-18]fluoride

Patent metadata

Field	Value
Publication number	US-11242314-B2
Application number	US-201715403954-A
Country	US
Kind code	B2
Filing date	Jan 11, 2017
Priority date	Jan 11, 2016
Publication date	Feb 8, 2022
Grant date	Feb 8, 2022

Abstract

The present disclosure relates to the methods for the preparation of reactive [F-18]fluoride in a form of [F-18]sulfonyl fluoride suitable for efficient radiolabeling without an azeotropic evaporation step by the use of anion exchange resin and sulfonyl chloride, and its applications in the manufacturing of PET radiopharmaceuticals.

First claim

What is claimed is:

1. A method of making [F-18]sulfonyl fluoride suitable as a source of [F-18] fluoride for use in a labeling reaction without further purification, wherein the method does not comprise an evaporation step, and wherein the method comprises:
a) passing an aqueous [F-18]fluoride solution or solvent through a solid phase extraction column comprising an anion-exchange resin so that the [F-18]fluoride is trapped on the resin;
b) rinsing the resin with an organic solvent to eliminate the residual water; and
c) eluting the [F-18]fluoride with an eluting solution to release the [F-18]fluoride from the anion-exchange resin as [F-18]RSO 2 F which acts as a source of [F-18]fluoride for the labeling reaction, wherein the eluting solution comprises a compound having the formula RSO 2 R 1 , a co-eluting agent, and an organic solvent, wherein
R is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, alkylaryl, substituted alkylaryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, arylalkynyl, substituted arylalkynyl, heteroaryl, substituted heteroaryl, methyl, trifluoromethyl, and combinations thereof; and
R 1 is a leaving group.

2. The method of claim 1 , wherein R is selected from the group consisting of alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, methyl and trifluoromethyl.

3. The method of claim 1 , wherein R is selected from the group consisting of CH 3 , CF 3 , C 6 H 5 , CH 3 C 6 H 4 , CF 3 C 6 H 4 , NO 2 C 6 H 4 , CIC 6 H 4 , FC 6 H 4 , BrC 6 H 4 , IC 6 H 4 , CH 3 COC 6 H 4 , MeOC 6 H 4 , CNC 6 H 4 , Me 2 NC 6 H 4 , 2,4,6-(CH 3 ) 3 C 6 H 2 , and C 5 H 5 N (pyridine).

4. The method of claim 1 , wherein R 1 is selected from the group consisting of Cl − , Br − , I − , tosylate (TsO), mesylate (MsO), and trifluoromethanesulfate (triflate; TfO).

5. The method of claim 1 , wherein RSO 2 is selected from the group consisting of tosyl (Ts), mesyl (Ms), trifluoromethanesulfonyl (Tf), nosyl (Ns), besyl (Bs), and N-phenyl-trifluoromethanesulfonimide (NTfPh).

6. The method of claim 1 , wherein RSO 2 R 1 is selected from the group consisting of tosyl chloride, mesyl chloride, trifluoromethanesulfonyl chloride, nosyl chloride, N-Phenyl-bis(trifluoromethanesulfonimide), tosyl anhydride, mesyl anhydride, trifluoromethanesulfonic anhydride, tosyl mesylate, and tosyl triflate.

7. The method of claim 1 , wherein the organic solvent is selected from the group consisting of acetonitrile, dimethylformamide, 2-amyl alcohol, tetrahydrofuran, and ethanol.

8. The method of claim 1 , wherein the eluting co-eluting agent is selected from the group consisting of TsOH/TsO − , MsOH/MsO − , TfOH/TfO − , HCl/Cl − , H 2 SO 4 − /HSO 4 − /SO 4 2− , AcOH/AcO − and TsOH.H 2 O.

9. The method of claim 1 , wherein the anion exchange resin comprises a polymeric matrix and quaternary ammonium groups.

10. The method of claim 1 , wherein the eluting is done via a back-and-forth method or a circulating method.

11. The method of claim 1 , further comprising regenerating the [F-18]fluoride in the presence of at least one base and at least one phase transfer catalyst during or before a labeling reaction.

12. The method of claim 11 , wherein the base is selected from the group consisting of potassium carbonate (K 2 CO 3 ), potassium bicarbonate (KHCO 3 ), cesium carbonate (Cs 2 CO 3 ), cesium biocarbonate, and tetrabutylammonium and tetramethylammonium salts (hydroxide, carbonate, and bicarbonate).

13. The method of claim 11 , wherein the base and phase transfer catalyst are pre-dried prior to use.

14. The method of claim 11 , wherein regeneration is carried out under anhydrous or aqueous conditions.

15. The method of claim 1 , wherein the [F-18]sulfonyl fluoride is used to measure concentration and specific activity of fluoride.

16. The method of claim 1 , wherein the eluted solution containing the [F-18]sulfonyl fluoride is used for the synthesis of a PET radiotracer.

17. The method of claim 16 , wherein (a) the [F-18]fluoride is regenerated prior to synthesis of the PET radiotracer by mixing (i) at least one base with or without at least one phase transfer catalyst and (ii) the [F-18]sulfonyl fluoride, and heating the mixture; or (b) the [F-18]fluoride is regenerated during synthesis of the PET radiotracer by mixing (i) at least one base with or without at least one phase transfer catalyst, (ii) the [F-18]sulfonyl fluoride, and (iii) an aliphatic or aromatic precursor, and heating the reaction mixture.

18. The method of claim 16 , wherein the PET radiotracer is selected from the group consisting of FDG, FLT, fallypride, FES, FFNP, FNOS, fluoroethyltosylate, fluoroethylazide, FC 9 COOMe, 4-fluorobenzaldehyde and 4-fluorobenzoate ethyl ester.

Assignees

• Zhou Dong
• Chu Wenhua
• Univ Washington

Inventors

• Zhou Dong
• Chu Wenhua

Classifications

• C07D213/52 Primary

  Sulfur atoms · CPC title

• C07B59/005

  Sugars; Derivatives thereof; Nucleosides; Nucleotides; Nucleic acids · CPC title

• C07D233/91

  Nitro radicals · CPC title

• C07B59/002

  Heterocyclic compounds · CPC title

• C07C67/307

  by introduction of halogen; by substitution of halogen atoms by other halogen atoms · CPC title