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Synthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([18F]FNT]) as a new class of tracer for imaging hypoxia

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Abstract

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([18F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl)-2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 °C. At the end of radiosynthesis, [18F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia.

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Acknowledgments

The project was supported by funding of Deutsche Forschungsgemeinschaft (DFG) with the grant no. MA 1096/8-1. We also gratefully acknowledge the support by DAAD-HEC (Deutscher Akademischer Austausch Dienst-Higher Education Commission, Pakistan; Reference No. 425, Codenumber A/06/19221) with a research grant.

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Authors and Affiliations

  1. Klinik für Nuklear Medizin, Universitäts-Klinikum, Ulm Universität, Albert-Einstein-Allee 23, 89081, Ulm, Germany

    Noeen Malik, Xian Lin, Christoph Solbach & Hans-Jürgen Machulla

  2. Institute of Radiopharmaceutical Sciences, Eidgenössische Technische Hochschule, Zürich, Switzerland

    Dirk Löffler

  3. Department of Radiology, Stanford University Medical Center, Stanford, USA

    Bin Shen

  4. Department for Preclinical Imaging and Radiopharmacy, University Hospital, Eberhard Karls University, Tübingen, Germany

    Gerald Reischl

  5. Interfacultary Institute for Biochemistry, Eberhard Karls University, Tübingen, Germany

    Wolfgang Voelter

Authors
  1. Noeen Malik
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  2. Xian Lin
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  3. Dirk Löffler
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  4. Bin Shen
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  5. Christoph Solbach
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  6. Gerald Reischl
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  7. Wolfgang Voelter
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  8. Hans-Jürgen Machulla
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Correspondence to Noeen Malik.

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Malik, N., Lin, X., Löffler, D. et al. Synthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([18F]FNT]) as a new class of tracer for imaging hypoxia. J Radioanal Nucl Chem 292, 1025–1033 (2012). https://doi.org/10.1007/s10967-012-1683-4

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  • DOI: https://doi.org/10.1007/s10967-012-1683-4

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