Radiosynthesis and biological evaluation of L and D S-(3-[18F]Fluoropropyl)-homocysteine for tumor imaging using positron emission tomography
No Thumbnail Available
Date
2011-03-24
Journal Title
Journal ISSN
Volume Title
Publisher
Americam Chemical Society
Abstract
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. © 2011, American Chemical Society.
Description
Keywords
Homocysteine, Proteins, Positron computed tomography, In vivo, Tyrosine, Impurities
Citation
Bourdier, T., Shepherd, R., Berghofer, P., Jackson, T., Fookes, C. J. R., Denoyer, D., Dorow, D. S., Greguric, I., Grégoire, M. C., Hicks, R. J., & Katsifis, A. Radiosynthesis and biological evaluation of L and D S-(3-[18F]Fluoropropyl)-homocysteine for tumor imaging using positron emission tomography. (2011). Journal of Medicinal Chemistry, 54 (6), 1860-1870. doi:10.1021/jm101513q