Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits |
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| Institution: | 1. Radiology & Nuclear Medicine, VU University Medical Center, 1081, HV, Amsterdam, The Netherlands;2. Anatomy & Neurosciences, VU University Medical Center, 1081, HV, Amsterdam, The Netherlands;3. ZEDIRA GmbH, D-64293, Darmstadt, Germany;1. Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing, China;2. Center of Parkinson''s Disease, Beijing Institute for Brain Disorders, Beijing, China;1. Danke Veterinary Clinic, Laprida 1502, Postal Code 1832 Lomas de Zamora Municipality, Buenos Aires Province, Argentina;2. Machipin Veterinary Clinic, Av. San Martín 1709, Postal Code 1846 Adrogué, Buenos Aires, Argentina |
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| Abstract: | 4-18F]2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-1-yl)-2-propanol (4-18F]fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2′-fluoro-4′-acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol in 19% yield. A modified Schiemann reaction on this product resulted in 4-18F]fluconazole with a radiochemical yield of 1.0–2.0% (EOS) within 2 h. 4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of 4-18F]fluconazole to a relatively uniform distribution of radioactivity in most organs. |
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