A non-anhydrous, minimally basic protocol for the simplification of nucleophilic 18F-fluorination chemistry

Abstract

Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [ 18 F]fluoride from an anion exchange cartridge with a basic solution of K 2 co 3 or KHCO 3 and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the water. In this work we describe an alternative "non-anhydrous, minimally basic" ("NAMB") technique that simplifies the process and avoids the basic conditions that can sometimes limit the scope and efficiency of [ 18 f] fluoride incorporation chemistry. In this approach, [ 18 f]f − is eluted from small (10-12 mg) anionexchange cartridges with solutions of tetraethylammonium bicarbonate, perchlorate or tosylate in polar aprotic solvents containing 10-50% water. After dilution with additional aprotic solvent, these solutions are used directly in nucleophilic aromatic and aliphatic 18 F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [ 18 f]ffrom the anion-exchange cartridge. As proof-of-principle, "NAMB" chemistry was utilized for the synthesis of the dopamine D 2 /D 3 antagonist [ 18 f]fallypride.

Novel late-stage radiosynthesis of 5-[18F]-trifluoromethyl-1,2,4-oxadiazole (TFMO) containing molecules for PET imaging

“…Remarkably, the use of cesium [ 18 F]fluoride (Cs[ 18 F]) led to a significantly improved radiochemical yield of 2–5%. Cs[ 18 F] has been used previously in halogen-exchange radiochemical reaction and cesium carbonate has been shown to facilitate certain nucleophilic [18F]fluorination reactions 41 – 43 .…”

18F-Fluorination Using Tri-Tert-Butanol Ammonium Iodide as Phase-Transfer Catalyst: An Alternative Minimalist Approach

“…Tetraethylammonium (TEA) hydrogen carbonate, tosylate, or perchlorate salts were developed by Inkster et al to avoid basic reaction conditions as well as azeotropic drying. Such PTC salts were efficiently used for both aliphatic and aromatic 18 F-fluorination reactions [10]. Apart from tetraalkylammonium salts, various arylonium salts, such as quaternary anilinium, diaryliodonium, and triarylsulfonium, were developed to minimalize the 18 F-labeling approach [13].…”

Highlight selection of radiochemistry and radiopharmacy developments by editorial board (January–June 2020)

“…Although this technique is reliable, it still has some limitations: some precursor and 18 F-labeled compounds are decomposed under basic conditions; variations in the drying step often influence the reproducibility of yields; and some [ 18 F]F − is lost due to volatilization and adsorption of the dried K[ 18 F]F onto the walls of the reaction vessel during the drying process. To eliminate these limitations, a “non-anhydrous, minimally basic” (NAMB) approaches that simplifies the process and avoid the basic condition was proposed (Inkster et al 2020 ) (Fig. 1 b).…”

“…X − = HCO 3 − , ClO 4 − , or OTs − . This figure was obtained from Inkster et al ( 2020 ) which was licensed under a Creative Commons License http://creativecommons.org/licenses/by/4.0/

Fig. 2 TCO-functionalized nanostars passively accumulate at the tumor site.

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