Radiosynthesis and Biological Evaluation of l- and d-S-(3-[18F]Fluoropropyl)homocysteine for Tumor Imaging Using Positro

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• 作者：Thomas Bourdier ; Rachael Shepherd ; Paula Berghofer ; Timothy Jackson ; Christopher J. R. Fookes ; Delphine Denoyer ; Donna S. Dorow ; Ivan Greguric ; Marie-Claude Gregoire ; Rodney J. Hicks ; Andrew Katsifis
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：March 24, 2011
• 年：2011
• 卷：54
• 期：6
• 页码：1860-1870
• 全文大小：970K
• 年卷期：v.54,no.6(March 24, 2011)
• ISSN：1520-4804

文摘

Interest in radiolabeled amino acids for metabolic imaging of cancer and limitations with [¹¹C]methionine has prompted the development of a new ¹⁸F-labeled methionine derivative S-(3-[¹⁸F]fluoropropyl)homocysteine ([¹⁸F]FPHCys). The l and d enantiomers of [¹⁸F]FPHCys were prepared from their respective protected S-(3-tosyloxypropyl)homocysteine precursors 1 by [¹⁸F]fluoride substitution using K_2.2.2 and potassium oxalate, followed by acid hydrolysis on a Tracerlab FX_FN synthesis module. [¹⁸F]-l-FPHCys and [¹⁸F]-d-FPHCys were isolated in 20 卤 5% radiochemical yield and >98% radiochemical and enantiomeric purity in 65 min. Competitive uptake studies in A375 and HT29 tumor cells suggest that l- and d-[¹⁸F]FPHCys are taken up by the l-transporter system. [¹⁸F]-l-FPHCys and [¹⁸F]-d-FPHCys displayed good stability In Vivo without incorporation into protein at least 2 h postinjection. Biodistribution studies demonstrate good uptake in A375 tumor-bearing rodents with tumor to blood ratios of 3.5 and 5.0 for [¹⁸F]-l-FPHCys and [¹⁸F]-d-FPHCys, respectively, at 2 h postinjection.