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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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Abstract

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.

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Acknowledgments

We thank Romana Meletta for the technical help with the RNA isolation and cDNA preparation.

Conflict of Interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences, ETH Zurich, Wolfgang-Pauli-Strasse 10, 8093, Zurich, Switzerland

    Adrienne Müller, Aristeidis Chiotellis, Claudia Keller, Simon M. Ametamey, Roger Schibli & Stefanie D. Krämer

  2. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland

    Roger Schibli & Linjing Mu

  3. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, Villigen, Switzerland

    Roger Schibli

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  1. Adrienne Müller
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  2. Aristeidis Chiotellis
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  3. Claudia Keller
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  4. Simon M. Ametamey
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  5. Roger Schibli
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  7. Stefanie D. Krämer
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Correspondence to Stefanie D. Krämer.

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Müller, A., Chiotellis, A., Keller, C. et al. Imaging Tumour ATB0,+ Transport Activity by PET with the Cationic Amino Acid O-2((2-[18F]fluoroethyl)methyl-amino)ethyltyrosine. Mol Imaging Biol 16, 412–420 (2014). https://doi.org/10.1007/s11307-013-0711-2

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  • DOI: https://doi.org/10.1007/s11307-013-0711-2

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