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Synthesis and preliminary biological evaluation of O -2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET) as a potential cationic amino acid PET tracer for tumor imaging

Chiotellis, Aristeidis ; Müller, Adrienne ; Weyermann, Karin ; Leutwiler, Dominique ; Schibli, Roger ; Ametamey, Simon ; Krämer, Stefanie ; Mu, Linjing

In: Amino Acids, 2014, vol. 46, no. 8, p. 1947-1959

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    Titre
    • Synthesis and preliminary biological evaluation of O -2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET) as a potential cationic amino acid PET tracer for tumor imaging
    Auteur
    • Chiotellis, Aristeidis. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Müller, Adrienne. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Weyermann, Karin. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Leutwiler, Dominique. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Schibli, Roger. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Ametamey, Simon. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Krämer, Stefanie. Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Zurich, Switzerland
    • Mu, Linjing. Department of Nuclear Medicine, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, University Hospital, Zurich, Switzerland
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:325977
    Summary
    Amino acid transport is an attractive target for oncologic imaging. Despite a high demand of cancer cells for cationic amino acids, their potential as PET probes remains unexplored. Arginine, in particular, is involved in a number of biosynthetic pathways that significantly influence carcinogenesis and tumor biology. Cationic amino acids are transported by several cationic transport systems including, ATB0,+ (SLC6A14), which is upregulated in certain human cancers including cervical, colorectal and estrogen receptor-positive breast cancer. In this work, we report the synthesis and preliminary biological evaluation of a new cationic analog of the clinically used PET tumor imaging agent O-(2-[18F]fluroethyl)-l-tyrosine ([18F]FET), namely O-2((2-[18F]fluoroethyl)methylamino)ethyltyrosine ([18F]FEMAET). Reference compound and precursor were prepared by multi-step approaches. Radiosynthesis was achieved by no-carrier-added nucleophilic [18F]fluorination in 16-20% decay-corrected yields with radiochemical purity >99%. The new tracer showed good stability in vitro and in vivo. Cell uptake assays demonstrated that FEMAET and [18F]FEMAET accumulate in prostate cancer (PC-3) and small cell lung cancer cells (NCI-H69), with an energy-dependent mechanism. Small animal PET imaging with NCI-H69 xenograft-bearing mice revealed good tumor visualization comparable to [18F]FET and low brain uptake, indicating negligible transport across the blood-brain barrier. In conclusion, the non-natural cationic amino acid PET probe [18F]FEMAET accumulates in cancer cells in vitro and in vivo with possible involvement of ATB0,+.