Catalytic radiofluorination

Patent metadata

Field	Value
Publication number	US-10098974-B2
Application number	US-201414552781-A
Country	US
Kind code	B2
Filing date	Nov 25, 2014
Priority date	Feb 24, 2004
Publication date	Oct 16, 2018
Grant date	Oct 16, 2018

Abstract

One aspect of the present invention relates to a method of preparing radiofluorinated substituted alkyl, cycloalkyl, aryl, and alkenyl compounds. In a preferred embodiment, potassium fluoride-18 is used. Another aspect of the invention relates to arylammonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the ammonium compound is a tetraaryl ammonium salt. Another aspect of the invention relates to arylsulfonium compounds containing fluorine-18 that are useful as imaging agents. In certain embodiments, the sulfonium compound is a triaryl sulfonium salt. Another aspect of the present invention relates to a method of obtaining a positron emission image of a mammal, comprising the steps of administering to a mammal a compound of the invention, and acquiring a positron emission spectrum of the mammal.

First claim

We claim:

1. A method of obtaining a positron emission image of a portion of a mammal, measuring blood flow in the heart of a mammal, or measuring membrane transport in a mammal, comprising the steps of:
administering to a mammal a compound represented by formula V; and
acquiring a positron emission spectrum of a portion of said mammal,
wherein the compound represented by formula V is:

wherein
R 1 represents independently for each occurrence optionally substituted phenyl;
R 2 is halogen-substituted phenyl, wherein said halogen substituent is 18 F; and
X is an anion that has an overall charge of −1.

2. The method of claim 1 , wherein said compound has a radioactivity of greater than or equal to about 1 Curie/mmol.

3. The method of claim 1 , wherein said compound has a radioactivity of greater than or equal to about 100 Curie/mmol.

4. The method of claim 1 , wherein R 1 is phenyl.

5. The method of claim 1 , wherein R 2 is 4- 18 F-fluorophenyl.

6. The method of claim 1 , wherein R 1 is phenyl and R 2 is 4- 18 F-fluorophenyl.

7. The method of claim 1 , wherein X is halide, acetate, or nitrate.

8. The method of claim 1 , wherein R 1 is phenyl, R 2 is 4- 18 F-fluorophenyl, and X is nitrate.

9. The method of claim 1 , wherein said mammal is a human, mouse, rat, dog, feline, monkey, guinea pig, or rabbit.

10. The method of claim 1 , wherein said mammal is a human.

11. A method of preparing (i) a fluorosubstituted aryl compound, or (ii) a fluorosubstituted alkenyl compound comprising the step of:
reacting potassium fluoride with
(i) a nitro aryl compound, wherein the nitro aryl compound does not contain an activing group or an electron-withdrawing group to enhance the reactivity of the nitro group, thereby forming a fluorosubstituted aryl compound that does not comprise a nitro group, or
(ii) an alkenyl halide or an alkenyl acetate, thereby forming a fluorosubstituted alkenyl compound.

12. The method of claim 11 , wherein the reaction is conducted in the presence of a crown ether.

13. The method of claim 12 , wherein the crown ether is selected from the group consisting of 1,4,10-trioxa-7,13-diaza-cyclopentadecane; 4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane; 4,7,13,16,21-pentaoxa-1,10-diazabicyclo[8.8.5]tricosane; and 4,7,13,18-tetraoxa-1,10-diazabicyclo[8.5.5]eicosane.

14. The method of claim 11 , wherein the potassium fluoride is potassium fluoride-18.

15. The method of claim 11 , wherein the reaction is conducted under microwave irradiation.

16. The method of claim 15 , wherein the reaction is run with or without a solvent.

17. The method of claim 15 , wherein the reaction is run with or without a catalyst.

18. The method of claim 1 , for obtaining a positron emission image of a portion of a mammal.

19. The method of claim 11 , for preparing a fluorosubstituted alkenyl compound.

Assignees

• Massachusetts Gen Hospital

Inventors

• Elmaleh David R
• Fischman Alan J
• Shoup Timothy M

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• A61K51/00

  Preparations containing radioactive substances for use in therapy or testing in vivo · CPC title

• C07C211/64

  having quaternised nitrogen atoms bound to carbon atoms of six-membered aromatic rings · CPC title

• C07F9/5442

  Aromatic phosphonium compounds (P-C aromatic linkage) · CPC title

• A61K51/0459

  having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine · CPC title