Radiosynthesis and Biological Evaluation of l - and d -S-(3-[18F]Fluoropropyl)homocysteine for Tumor Imaging Using Positron Emission Tomography
| Autor: | Donna S. Dorow, Thomas Bourdier, Christopher J. R. Fookes, Timothy Jackson, Delphine Denoyer, Rachael Shepherd, Andrew Katsifis, Paula Berghofer, Marie-Claude Gregoire, Rodney J. Hicks, Ivan Greguric |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Fluorine Radioisotopes
Biodistribution Amino Acid Transport System A Homocysteine Stereochemistry Mice Nude Mice Structure-Activity Relationship chemistry.chemical_compound In vivo Cell Line Tumor Drug Discovery Animals Humans Tissue Distribution chemistry.chemical_classification Mice Inbred BALB C Methionine Radiochemistry Radiosynthesis Stereoisomerism Neoplasms Experimental Amino acid chemistry Positron-Emission Tomography Amino Acid Transport System L Molecular Medicine Acid hydrolysis Radiopharmaceuticals Enantiomer |
| Zdroj: | Journal of Medicinal Chemistry. 54:1860-1870 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Interest in radiolabeled amino acids for metabolic imaging of cancer and limitations with [(11)C]methionine has prompted the development of a new (18)F-labeled methionine derivative S-(3-[(18)F]fluoropropyl)homocysteine ([(18)F]FPHCys). The L and D enantiomers of [(18)F]FPHCys were prepared from their respective protected S-(3-tosyloxypropyl)homocysteine precursors 1 by [(18)F]fluoride substitution using K(2.2.2) and potassium oxalate, followed by acid hydrolysis on a Tracerlab FX(FN) synthesis module. [(18)F]-L-FPHCys and [(18)F]-D-FPHCys were isolated in 20 ± 5% radiochemical yield and98% radiochemical and enantiomeric purity in 65 min. Competitive uptake studies in A375 and HT29 tumor cells suggest that L- and D-[(18)F]FPHCys are taken up by the L-transporter system. [(18)F]-L-FPHCys and [(18)F]-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 [(18)F]-L-FPHCys and [(18)F]-D-FPHCys, respectively, at 2 h postinjection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|