Routine quality control of recycled target [ 18 O]water by capillary electrophoresis and gas chromatography Bill X. Huang*, Michael A. Channing, Paul S. Plascjak, Dale O. Kiesewetter, Margaret Der, Ying Ma, William C. Eckelman PET Department, Warren G. Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, 20892 USA Received 19 March 2003; accepted 14 May 2003 Abstract Recycling of [ 18 O]water for [ 18 F]fluoride production can be accomplished with reliable results. We have developed sensitive, robust, and rapid analyses of impurities in [ 18 O]water. Anions were quantitated by capillary electrophoresis and organic residuals were quantitated by gas chromatography using methods with excellent reproducibility and linearity. Kryptofix 222 (K-222) was quantitated by a sensitive LC-MS-MS technique. Isotopic composition was determined by GC-MS with satisfactory accuracy and precision. These methods were employed to evaluate recovered [ 18 O]water purified by a novel electrolysis method. 2-[ 18 F]FDG yields using purified [ 18 O]water with very low levels of impurities are indistinguishable from newly purchased [ 18 O]water. High ( 300 ppm) carbonate concentration reduces the fluoride trapping efficiency of QMA. The analyses of anions, organics, and isotopic enrichment were applied routinely for quality control of [ 18 O]water to predict a satisfactory outcome of 2-[ 18 F]FDG production. Published by Elsevier Inc. All rights reserved. Keywords: Target [ 18 O]water; Quality control; Capillary electrophoresis; Gas chromatography 1. Introduction The most commonly used synthesis of 2-[ 18 F]FDG em- ploys nucleophilic substitution of no-carrier-added [ 18 F]fluoride on 1,3,4,6-tetra-O-acetyl-2-O-trifluorometh- anesulfonyl--D-mannopyranose [13]. [ 18 F]Fluoride ion is commonly produced from proton irradiation of [ 18 O]water. Numerous studies have suggested that ionic contaminants originating from the [ 18 O]water target affect the [ 18 F]fluo- ride chemistry, resulting in low and variable radiofluorina- tion yields [3,4,5,8,10,11,19,29,31,33]. Metal ions in target water may reduce the availability of reactive fluoride by forming inactive metal-fluoride complexes. Inorganic and organic anions may compete with fluoride in the displace- ment reaction. In addition, organic impurities may cause target pressure buildup, damage the target, and form radi- olysis products that lower the fluorination yield [2,9,24,30]. Therefore, the quality of target [ 18 O]water is important for the effectiveness of 2-[ 18 F]FDG synthesis. Due to the limited supply and high cost of [ 18 O]water, PET centers often recycle target water. The first step is to separate the [ 18 F]fluoride from [ 18 O]water. Various tech- niques for separation have been studied and successfully used for 2-[ 18 F]FDG synthesis [1,6,12,15,16,17,25,26,28]. The [ 18 O]water is then collected and purified by distillation. Chaly et al. have modified their preparative procedure and recovered the [ 18 O]water by direct distillation during their 2-[ 18 F]FDG synthesis [6]. In their study, the collected [ 18 O]water was successfully reused for 2 to 3 consecutive runs, but a 5% reduction of [ 18 F]fluoride activity was ob- served. One major concern of distillation is the inability to completely remove residual organics [24]. Purification by photochemical combustion, reported by Mangner et al., has been successful in removing organics [24]. In this method, the recycled [ 18 O]water was irradiated with ultraviolet light to oxidize the organic impurities. Fractional distillation of the resulting solution effectively removed the organic oxi- dation products. The recycled water purified in this way achieved the same yield for 2-[ 18 F]FDG as new [ 18 O]water and resulted in less than 10% reduction in isotopic enrich- ment. In this paper we describe our electrolysis method for the * Corresponding author. Tel.: +1-301-435-8502; fax: +1-301-402- 3521. E-mail address: bhuang@mail.cc.nih.gov (B.X. Huang). Nuclear Medicine and Biology 30 (2003) 785–790 www.elsevier.com/locate/nucmedbio 0969-8051/03/$ – see front matter Published by Elsevier Inc. All rights reserved. doi:10.1016/S0969-8051(03)00083-0