Catalytic radiofluorination
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.
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.