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Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine |
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| Authors: | Adrienne Müller Aristeidis Chiotellis Claudia Keller Simon M Ametamey Roger Schibli Linjing Mu Stefanie D Krämer |
| Institution: | 1. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland 2. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland 3. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen, Switzerland |
| Abstract: | PurposeThe 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.ProceduresCell 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.Results18F]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.ConclusionATB0,+ activity can be imaged in vivo by PET with 18F]FEMAET. |
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