Synthesis
18F-FDG was first synthesized via electrochemical fluorination. Subsequently, a nucleophilic synthesis was devised. Here, radioactive 18F must be made first as the fluoride anion in the cyclotron. This may be accomplished by bombardment of neon-20 with deuterons, but usually is done by proton bombardment of 18O-enriched water, causing a (p,n) reaction (sometimes called a "knockout reaction"—a common type of nuclear reaction with high probability) in the 18O. This produces "carrier-free" dissolved 18F-fluoride (18F–) ions in the water. The 109.8 minute half-life of 18F makes rapid and automated chemistry necessary after this point.
To do this chemistry, the 18F– is separated from the aqueous solvent by trapping it on an ion-exchange column, and eluted with an acetonitrile solution of 2,2,2-cryptand and potassium carbonate, which gives + 18F− (2) when dried.
The fluoride anion is not ordinarily very nucleophilic. Anhydrous conditions are required to avoid the competing reaction with hydroxide. The use of the cryptand to sequester the potassium ions avoids ion-pairing between free potassium and fluoride ions, making the fluoride anion more reactive.
Intermediate 2 is reacted with a protected mannose triflate (1); the fluoride anion displaces the triflate leaving group in an SN2 reaction, giving the protected fluorinated deoxyglucose (3). Base hydrolysis removes the acetyl protecting groups, giving the desired product (4) after removing the cryptand via ion-exchange:
Read more about this topic: Fludeoxyglucose (18F)
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