title: Radiosynthesis and biological evaluation of L- and D-S-(3-[18F]fluoropropyl)homocysteine for tumor imaging using positron emission tomography.
abstract: 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 and >98% 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.
authors.affiliation: ANSTO LifeSciences, Australian Nuclear Science and Technology Organisation, Locked Bag 2001, Kirrawee DC, NSW, 2232, Sydney, Australia. bts@ansto.gov.au
authors.forename: Thomas
authors.initials: T
authors.lastname: Bourdier
authors.forename: Rachael
authors.initials: R
authors.lastname: Shepherd
authors.forename: Paula
authors.initials: P
authors.lastname: Berghofer
authors.forename: Timothy
authors.initials: T
authors.lastname: Jackson
authors.forename: Christopher J R
authors.initials: CJ
authors.lastname: Fookes
authors.forename: Delphine
authors.initials: D
authors.lastname: Denoyer
authors.forename: Donna S
authors.initials: DS
authors.lastname: Dorow
authors.forename: Ivan
authors.initials: I
authors.lastname: Greguric
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gregoire
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Hicks
authors.forename: Andrew
authors.initials: A
authors.lastname: Katsifis
mesh_terms: D026924:Amino Acid Transport System A / Q000037:antagonists & inhibitors / Q000378:metabolism; D027062:Amino Acid Transport System L / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D026924:Amino Acid Transport System A; D027062:Amino Acid Transport System L; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; C558745:S-(3-fluoropropyl)homocysteine; D006710:Homocysteine