title: Fully automated synthesis of [18F]fluoromisonidazole using a conventional [18F]FDG module.
abstract: We developed a new fully automated method for the synthesis of [18F]fluoromisonidazole ([18F]FMISO) by modifying a commercial FDG synthesizer and its disposable fluid pathway. A three-step procedure was used to prepare the tosylate precursor, 1-(2'-nitro-1'-imidazolyl)-2-O-tetrahydrofuranyl-3-O-toluenesulfonylpropanediol. Using glycerol as the starting material, the precursor was synthesized with a yield of 21%. The optimal labeling conditions for the automated synthesis of [18F]FMISO was 10 mg of precursor in acetonitrile (2 ml heated at 105 degrees C for 360 s, followed by heating at 75 degrees C for 280 s and hydrolysis with 1 N HCl at 105 degrees C for 300 s. Using 3.7 GBq of [18F]F- as a starting activity, [18F]FMISO was obtained with high end-of-synthesis (EOS) radiochemical yields of 58.5+/-3.5% for 60.0+/-5.2 min with high-performance liquid chromatography (HPLC) purification. When solid-phase purification steps were added, the EOS radiochemical yields were 54.5+/-2.8% (337+/-25 GBq/micromol) for 70.0+/-3.8 min (n=10 for each group, decay-corrected). With a high starting radioactivity of 37.0 GBq, we obtained radiochemical yields of 54.4+/-2.9% and 52.8+/-4.2%, respectively (n=3). The solid-phase purification removed unreacted [18F]fluoride and polar impurities before the HPLC procedure. Long-term tests showed a good stability of 98.2+/-1.5%. This new automated synthesis procedure combines high and reproducible yields with the advantage of using a disposable cassette system.
authors.affiliation: Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap-dong, Songpa-gu, Seoul 138-736, South Korea. sjoh@amc.seoul.kr
authors.forename: Seung Jun
authors.initials: SJ
authors.lastname: Oh
authors.forename: Dae Yoon
authors.initials: DY
authors.lastname: Chi
authors.forename: Christoph
authors.initials: C
authors.lastname: Mosdzianowski
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hee Seop
authors.initials: HS
authors.lastname: Gil
authors.forename: Se Hun
authors.initials: SH
authors.lastname: Kang
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Ryu
authors.forename: Dae Hyuk
authors.initials: DH
authors.lastname: Moon
mesh_terms: D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004867:Equipment Design; D019544:Equipment Failure Analysis; D019788:Fluorodeoxyglucose F18 / Q000032:analysis / Q000737:chemistry; D008920:Misonidazole / Q000031:analogs & derivatives* / Q000032:analysis / Q000138:chemical synthesis; D019275:Radiopharmaceuticals / Q000032:analysis / Q000138:chemical synthesis; D012371:Robotics / Q000295:instrumentation* / Q000379:methods*; D013194:Staining and Labeling / Q000295:instrumentation* / Q000379:methods*
chemical_list: D019275:Radiopharmaceuticals; C031843:fluoromisonidazole; D019788:Fluorodeoxyglucose F18; D008920:Misonidazole