Radiosynthesis and biological evaluation of L and D S-(3-[18F]Fluoropropyl)-homocysteine for tumor imaging using positron emission tomography

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.

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