Synthesis of 18F-labeled Tracers in Hydrous Organic Solvents

• US 20130005956A1
• Filed: 04/08/2011
• Published: 01/03/2013
• Est. Priority Date: 04/08/2010
• Status: Active Grant

• Current Assignee: Siemens Medical Solutions USA Incorporated (Siemens AG)
• Original Assignee: Siemens Medical Solutions USA Incorporated (Siemens AG)
• Inventors: Gangadharmath, Umesh, Walsh, Joseph, Kolb, Hartmuth
• Granted Patent: US 9,023,316 B2
• Time in Patent Office: Days
• US Class Current: 536/28.2
• CPC Class Codes: A61K 51/04 Organic compounds
• CPC Class Codes: A61K 51/0448 tropane or nortropane groups, e.g. cocaine
• CPC Class Codes: A61K 51/0453 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61K 51/0459 having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
• CPC Class Codes: A61K 51/047 Benzodiazepines
• CPC Class Codes: A61K 51/0491 Sugars, nucleosides, nucleotides, oligonucleotides, nucleic acids, e.g. DNA, RNA, nucleic acid aptamers
• CPC Class Codes: B01D 15/363 Anion-exchange

Abstract

A method for synthesizing an ¹⁸F-labeled probe. The method includes a step of eluting an amount of ¹⁸F with a first solvent which includes a predetermined amount of water and at least one organic solvent. In this step, the ¹⁸F elutes as an ¹⁸F solution. The method also includes a step of using the ¹⁸F solution to perform ¹⁸F-labeling in the presence of at least one labeling reagent and at least one phase transfer catalyst so as to generate the ¹⁸F-labeled probe. In the method, there is no step of drying the ¹⁸F starting from a time when the eluting step is performed and ending at a time when the ¹⁸F-labeling step is performed.

Claims

1. A method for synthesizing an ¹⁸F-labeled probe the method comprising:

a step of eluting an amount of ¹⁸F with a first solvent which comprises a predetermined amount of water and at least one organic solvent, the ¹⁸F eluting as an ¹⁸F solution; and

a step of using the ¹⁸F solution to perform ¹⁸F-labeling in the presence of at least one labeling reagent and at least one phase transfer catalyst so as to generate the ¹⁸F-labeled probe;

wherein there is no step of drying the ¹⁸F starting from a time when the eluting step is performed and ending at a time when the ¹⁸F-labeling step is performed.

2. The method of claim 1;

wherein the first solvent further comprises the at least one labeling reagent and the at least one phase transfer catalyst.

3. The method of claim 1;

wherein a total amount of water in the ¹⁸F solution is in a range of about 0.1% to about 5.0%.

4. The method of claim 1;

wherein the ¹⁸F-labeling step includes combining the ¹⁸F solution with a probe precursor so as to arrive at an ¹⁸F-labeling solution with a total amount of water in a range of about 0.1% to about 2.0%.

5. The method of claim 4;

wherein the ¹⁸F-labeling step further includes diluting at least one of the ¹⁸F solution and the probe precursor with an organic solvent so that, when the ¹⁸F solution and the probe precursor are combined, the ¹⁸F-labeling solution has the total amount of water in the range of about 0.1% to about 2.0%.

6. The method of claim 1;

wherein the at least one labeling reagent is selected from the group consisting of K₂CO₃, KHCO₃, Cs₂CO₃, potassium mesylate, potassium oxylate, and tetrabutylammonium bicarbonate.

7. The method of claim 1;

wherein the at least one phase transfer catalyst is Kryptofix K222.

8. The method of claim 1;

wherein the organic solvent includes a polar aprotic solvent.

9. The method of claim 8;

wherein the polar aprotic solvent is selected from the group consisting of acetonitrile, dimethyl sulfoxide (“

DMSO”

), tetrahydrofuran (“

THF”

), dimethylformamide (“

DMF”

), N-methylpyrrolidone (“

NMP”

), and dioxane.

10. The method of claim 1;

wherein the organic solvent includes a polar protic solvent.

11. The method of claim 10;

wherein the polar protic solvent is selected from the group consisting of tBuOH and t-amyl alcohol.

12. The method of claim 1;

wherein the ¹⁸F-labeled probe generate is selected from the group consisting of ¹⁸F-FDG, ¹⁸F-HX4, ¹⁸F-FLT, ¹⁸F-MISO, ¹⁸F-FAZA, ¹⁸F-Fallypride, ¹⁸F-FHBG, ¹⁸F-FHPG, ¹⁸F-4-fluorobenzaldehyde, ¹⁸F-4-fluoroethylbenzoate, ¹⁸F-4-fluoromethyl benzoate, ¹⁸F-fluoroethylazide, and ¹⁸F-W372.

13. The method of claim 1;

wherein the ¹⁸F-labeled probe generate is ¹⁸F-VM4-037.

15. The solution of claim 13, further comprising:

at least one labeling reagent; and

at least one phase transfer catalyst.

14. A solution for use in synthesizing an ¹⁸F-labeled probe, the solution comprising:

an amount of ¹⁸F;

water; and

at least one organic solvent;

wherein a total amount of water in the solution is in a range of about 0.1% to about 5.0%.

16. The solution of claim 14, further comprising:

a probe precursor;

wherein the total amount of water in the solution is in a range of about 0.1% to about 2.0%.