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

• Published in: Journal of medicinal chemistry 2011-03, Vol.54 (6), p.1860-1870
• Main Authors: Bourdier, Thomas, Shepherd, Rachael, Berghofer, Paula, Jackson, Timothy, Fookes, Christopher J. R, Denoyer, Delphine, Dorow, Donna S, Greguric, Ivan, Gregoire, Marie-Claude, Hicks, Rodney J, Katsifis, Andrew
• Format: Article
• Language: English
• Subjects: Amino Acid Transport System A - antagonists & inhibitors; Amino Acid Transport System A - metabolism; Amino Acid Transport System L - antagonists & inhibitors; Amino Acid Transport System L - metabolism; Animals; Cell Line, Tumor; Fluorine Radioisotopes; Homocysteine - analogs & derivatives; Homocysteine - chemical synthesis; Homocysteine - chemistry; Homocysteine - pharmacokinetics; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms, Experimental - diagnostic imaging; Neoplasms, Experimental - metabolism; Positron-Emission Tomography; Radiopharmaceuticals - chemical synthesis; Radiopharmaceuticals - chemistry; Radiopharmaceuticals - pharmacokinetics; Stereoisomerism; Structure-Activity Relationship; Tissue Distribution
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm101513q

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 K2.2.2 and potassium oxalate, followed by acid hydrolysis on a Tracerlab FXFN synthesis module. [18F]-l-FPHCys and [18F]-d-FPHCys were isolated in 20 ± 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.