title: Imaging tumour ATB0,+ transport activity by PET with the cationic amino acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine.
abstract: OBJECTIVE
  The concentrative amino acid transporter ATB(0,+) (SLC6A14) is under evaluation as a target for anticancer therapy. An ATB(0,+)-selective positron emission tomography (PET) probe could advance preclinical drug development. We characterised the cationic tyrosine analogue O-2((2-[(18)F]fluoroethyl)methyl-amino)ethyltyrosine ([(18)F]FEMAET) as a PET probe for ATB(0,+) activity.
  
  
  METHODS
  Cell uptake was studied in vitro. ATB(0,+) expression was quantified by real-time PCR. [(18)F]FEMAET accumulation in xenografts was investigated by small animal PET with mice.
  
  
  RESULTS
  [(18)F]FEMAET accumulated in PC-3 and NCI-H69 cancer cells in vitro. As expected for ATB(0,+) transport, uptake was inhibited by LAT/ATB(0,+) inhibitors and dibasic amino acids, and [(18)F]FEMAET efflux was only moderately stimulated by extracellular amino acids. ATB(0,+) was expressed in PC-3 and NCI-H69 but not MDA-MB-231 xenografts. PET revealed accumulation in PC-3 and NCI-H69 xenografts and significant reduction by ATB(0,+) inhibition. Uptake was negligible in MDA-MB-231 xenografts.
  
  
  CONCLUSIONS
  ATB(0,+) activity can be imaged in vivo by PET with [(18)F]FEMAET.
authors.affiliation: Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Müller
authors.forename: Aristeidis
authors.initials: A
authors.lastname: Chiotellis
authors.forename: Claudia
authors.initials: C
authors.lastname: Keller
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Roger
authors.initials: R
authors.lastname: Schibli
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.forename: Stefanie D
authors.initials: SD
authors.lastname: Krämer
mesh_terms: D026905:Amino Acid Transport Systems / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D005462:Fluorine Radioisotopes / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D050480:Plasma Membrane Neurotransmitter Transport Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D026905:Amino Acid Transport Systems; D005462:Fluorine Radioisotopes; D050480:Plasma Membrane Neurotransmitter Transport Proteins; C532353:Slc6A14 protein, mouse; D014443:Tyrosine