Abstract
Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [18F]fluoride from an anion exchange cartridge with a basic solution of K2CO3 or KHCO3 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 [18F]fluoride incorporation chemistry. In this approach, [18F]F− is eluted from small (10–12 mg) anion-exchange 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 18F-fluorination reactions, obviating the need for azeotropic drying. Perchlorate and tosylate are minimally basic anions that are nevertheless suitable for removal of [18F]F- from the anion-exchange cartridge. As proof-of-principle, “NAMB” chemistry was utilized for the synthesis of the dopamine D2/D3 antagonist [18F]fallypride.
Highlights
Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [18F]fluoride from an anion exchange cartridge with a basic solution of K2CO3 or KHCO3 and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the water
Considering that some 18F Positron Emission Tomography (PET) tracers suffer from low isolated yields due to the sensitivity of the precursor or product to heating in the presence of HCO3− or CO32−, we evaluated tetraethylammonium perchlorate (TEAP) and tetraethylammonium p-toluenesulfonate (TEATos) as minimally basic alternatives to tetraethylammonium bicarbonate (TEAB)
Solutions of tetraethylammonium tosylate and tetraethylammonium perchlorate in non-anhydrous solvent mixtures offer a straightforward means to efficiently extract [18F]F− from small AEX columns and facilitate the synthesis of 18F-labeled aromatic and aliphatic compounds without the need for the azeotropic drying step that is ubiquitous in 18F-PET chemistry
Summary
Fluorine-18 radiolabeling typically includes several conserved steps including elution of the [18F]fluoride from an anion exchange cartridge with a basic solution of K2CO3 or KHCO3 and Kryptofix 2.2.2. in mixture of acetonitrile and water followed by rigorous azeotropic drying to remove the water. After the [18F]F− has been dried, a solution of the precursor compound in an anhydrous solvent is added to the dried [18F]F−, and the reaction mixture is heated to produce the desired product.
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