[18F]Fluoropyruvate: radiosynthesis and initial biological evaluation |
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| Authors: | Keith Graham Andre Müller Lutz Lehmann Norman Koglin Ludger Dinkelborg Holger Siebeneicher |
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| Affiliation: | 1. Bayer Healthcare, Global Drug Discovery, Berlin, Germany;2. Piramal Imaging, Berlin, Germany |
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| Abstract: | The radiosynthesis of [18F]fluoropyruvate was investigated using numerous precursors were synthesized from ethyl 2,2‐diethoxy‐3‐hydroxypropanoate (5) containing different leaving groups: mesylate, tosylate, triflate, and nonaflate. These precursors were evaluated for [18F]fluoride incorporation with triflate being superior. The subsequent hydrolysis step was investigated, and an acidic hydrolysis was optimized. After establishing suitable purification and formulation methods, the [18F]fluoropyruvate could be isolated in ca. 50% d.c. yield. The [18F]fluoropyruvate was evaluated in vitro for its uptake into tumor cells using adenocarcinomic human alveolar basal epithelial cells (A549) and unfortunately showed an uptake of approximately 0.1% of the applied dose per 100,000 cells after 30 min. Initial pharmacokinetic properties were assessed in vivo using nude mice showed a high degree of bone uptake from defluorination, which will limit its potential as an imaging agent for metabolic processes. Copyright © 2014 John Wiley & Sons, Ltd. |
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| Keywords: | fluorine‐18 radiolabeling PET imaging fluoropyruvate pyruvate kinase pyruvate dehydrogenase |
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