[¹⁸F]/¹⁹F exchange in fluorine containing compounds for potential use in ¹⁸F‐labelling strategies

Abstract

Exchange of [18 F]fluoride with 19 F in various organofluorine compounds in concentrations ranging from 0.06 to 56 mM was explored. We aimed to explore whether exchange reactions can be a potential useful labelling strategy, when there are no requirement of high specific radioactivity. Parameters such as solvents, temperature, conventional vs microwave heating, and the degree of fluorine load in some aromatic and alkyl compounds were investigated with regard to radiochemical yield and specific radioactivity. A series of fluorobenzophenones (1-6), 1-(4-fluorophenyl)ethanone (7), various activated and deactivated fluoro benzenes (8-16), N-(pentafluorophenyl)benzamide (17), (pentafluorophenyl)formamide (18) (23), 2,5,6,7,8-pentafluoro-3-methylnaphthoquinone (24) and 1-(2,4-difluorophenyl)-3-(4-fluorophenyl)-propan-1-one (25) were investigated. The multi-fluorinated molecules containing an electron-withdrawing group were successfully labelled at room temperature, whereas the monofluorinated, as well as those containing an electron-donating group, required heating for the exchange reaction to take place.

19F/18F exchange synthesis for a novel [18F]S1P3‐radiopharmaceutical

“…The 19 F/ 18 F isotope exchange reaction was performed using relatively harsh conditions. The large substituent attached at the para position of the 1,2‐difluorobenzene ring of 1 reduces reactivity of the benzene ring and makes the isotope exchange reaction difficult, an outcome that has been demonstrated earlier with similar compounds . Using the present reaction conditions, we observed that the chemical decomposition of the precursor and also [ 18 F] 1 is rapid (Figure ).…”

“…Previously, direct 19 F/ 18 F isotope exchange reactions have been applied to 18 F‐fluorination of small aromatic molecules. 18 F‐Labeling of larger molecules with 19 F/ 18 F isotope exchange reaction has been reported to be more difficult, and commonly, these molecules have been produced with at least a two‐step synthesis where protecting groups were needed or by coupling a 18 F‐labeled small molecule with a larger molecule . In this study, [ 18 F] 1 was synthesized using one‐step synthesis and 19 F/ 18 F isotope exchange reaction (Figure ).…”

“…The 19 F/ 18 F isotope exchange reaction allows the labeling of drug molecules that contain fluorine in their molecular structure. Several 19 F/ 18 F isotope exchange studies examined the effects of the molecular structure of the precursor and have investigated the reaction kinetic parameters to optimize radiochemical yield and specific activity . Most of these studies have been performed using relatively small amounts of initial activity of 18 F‐fluorine, and precursor compounds have mostly been relatively simple small molecules …”

Synthesis of meta-substituted [18F]3-fluoro-4-aminopyridine via direct radiofluorination of pyridine N-oxides

“…Even more remarkable is that this reaction reaches equilibrium within seconds. Fluorine exchange in organic compounds has been reported before 15 , however, to our knowledge this is the first example of fluoride exchange of a C-F bond in a heterocyclic compound.…”

Novel Method for Radiolabeling and Dimerizing Thiolated Peptides Using 18F-Hexafluorobenzene

“…The published radiosynthesis of 18 F-HFB (Figure 2) 13 was adapted for automation on a modular system (Eckert and Ziegler). The synthesis was conducted at room temperature (RT) in dimethyl sulfoxide (DMSO) and quantities of K 2 CO 3 , K 2.2.2 , and HFB were adjusted in order to achieve good yields using the lowest amount of HFB (Table 1).…”