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Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O -2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine

Müller, Adrienne ; Chiotellis, Aristeidis ; Keller, Claudia ; Ametamey, Simon ; Schibli, Roger ; Mu, Linjing ; Krämer, Stefanie

In: Molecular Imaging and Biology, 2014, vol. 16, no. 3, p. 412-420

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    Title
    • Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O -2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine
    Author
    • Müller, Adrienne. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    • Chiotellis, Aristeidis. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    • Keller, Claudia. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    • Ametamey, Simon. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    • Schibli, Roger. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    • Mu, Linjing. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland
    • Krämer, Stefanie. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Molecular Imaging and Biology, 2014, vol. 16, no. 3, p. 412-420. Springer US; http://www.springer-ny.com
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:324765
    Summary
    Purpose: The concentrative amino acid transporter ATB0,+ (SLC6A14) is under evaluation as a target for anticancer therapy. An ATB0,+-selective positron emission tomography (PET) probe could advance preclinical drug development. We characterised the cationic tyrosine analogue O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine ([18F]FEMAET) as a PET probe for ATB0,+ activity. Procedures: Cell uptake was studied in vitro. ATB0,+ expression was quantified by real-time PCR. [18F]FEMAET accumulation in xenografts was investigated by small animal PET with mice. Results: [18F]FEMAET accumulated in PC-3 and NCI-H69 cancer cells in vitro. As expected for ATB0,+ transport, uptake was inhibited by LAT/ATB0,+ inhibitors and dibasic amino acids, and [18F]FEMAET efflux was only moderately stimulated by extracellular amino acids. ATB0,+ 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 ATB0,+ inhibition. Uptake was negligible in MDA-MB-231 xenografts. Conclusion: ATB0,+ activity can be imaged in vivo by PET with [18F]FEMAET.