Chemistry of fluorine-18 radiopharmaceuticals

PET Designated Flouride-18 Production and Chemistry

“…[ 18 F]-F 2 fluoride gas produced in the cyclotron can be directly used for electrophilic fluorination, or alternatively be used as a progenitor of other fluorination reagents. Fluoride is a violently reactive gas that erratically reacts with organic molecules to give poor regioselectivity and mixtures of products that result from the addition across the double bond [15, 28, 29] The use of fluoride diluted with an inert gas gives a more controllable reagent that can react selectively with organic compounds. If the double bond is substituted with electron donating groups, the intermediate cation is more stable, resulting in less product mixtures.…”

“…If the double bond is substituted with electron donating groups, the intermediate cation is more stable, resulting in less product mixtures. In addition, substitution of arenes with organometallic precursor, can afford higher and further specific regioselectivity during the electrophilic fluorination [15, 28-30]. Therefore, it is important to take into account the biological system that is being investigated when using [ 18 F]-F 2, since increasing the yield of [ 18 F]-F 2 by adding carrier will result in very low specific activity.…”

“…Another alternative for the use of the reactive F 2 electrophile is to convert it to the less vigorous electrophile, acetyl hypofluorite (AcOF) [15, 31]. [ 18 F]-F 2 is produced by either of the two methods described above, and subsequently converted to [ 18 F]-AcOF by passing through a CH 3 CO 2 Na·3H 2 O-column.…”

“…The presence of electron-withdrawing groups, such as cyano, trifluoromethyl, aldehydes, ketones and nitro, in the ortho and para positions on the aromatic ring decreases the electron density, which allows sufficient activation for the nucleophilic substitution [15]. It is also feasible to perform isotopic exchange, [ 19 F]fluoride to [ 18 F]fluoride, however, the specific activity will be low.…”

“…18 F is readily produced in a reactor or on a cyclotron using a variety of nuclear reactions and can be produced with the theoretical specific activity value of 1710 Ci/μmol [13-15]. The specific activity of the tracer, which reflects the radiolabeled fraction out of the total administered mass, should be high enough to avoid saturation of binding-sites or toxicity to the biological system.…”