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Journal of Radioanalytical and Nuclear Chemistry

, Volume 292, Issue 3, pp 1025–1033 | Cite as

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

  • Noeen Malik
  • Xian Lin
  • Dirk Löffler
  • Bin Shen
  • Christoph Solbach
  • Gerald Reischl
  • Wolfgang Voelter
  • Hans-Jürgen Machulla
Article

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.

Keywords

Radiofluorinations p-tyrosine with 2-nitroimidazole Hypoxia imaging 

Notes

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.

References

  1. 1.
    Machulla H-J (1999) Imaging of hypoxia: tracer developments. Kluwer Academic Publishers, 33: p-15Google Scholar
  2. 2.
    Grierson JR, Link JM, Mathis CA, Rasey JS, Krohn KAJ (1989) Nucl Med 30(3):343–350Google Scholar
  3. 3.
    Piert M, Machulla H-J, Becker G, Stahlschmidt A, Patt M, Aldinger P, Dissmann PD, Fischer H, Bares R, Becker HD, Lauchart W (1999) Eur J Nucl Med 26(2):95–109CrossRefGoogle Scholar
  4. 4.
    Piert M, Machulla H-J, Becker G, Aldinger P, Winter E, Bares R (2000) Nucl Med Biol 27(8):693–700CrossRefGoogle Scholar
  5. 5.
    Reischl G, Ehrlichmann W, Bieg C, Solbach C, Kumar P, Wiebe L, Machulla H-J (2005) Appl Radiat Isot 62(6):701–897CrossRefGoogle Scholar
  6. 6.
    Reischl G, Sabbah A, Machulla H-J (2007) J Nucl Med 48(Supplement-2):325PGoogle Scholar
  7. 7.
    Krohn KA, Link JM, Mason RPJ (2008) Nucl Med 49(Supplement-2):129S–148SCrossRefGoogle Scholar
  8. 8.
    Jain-Vakkalagadda B, Dey S, Pal D, Mitra AK (2003) Investig Ophthalmol Vis Sci 44(7):2919–2927CrossRefGoogle Scholar
  9. 9.
    Uchino H, Kanai Y, Kim DK, Wempe MF, Chairoungdua A, Morimoto E, Anders MW, Endou H (2002) Mol Pharmacol 61:729–737CrossRefGoogle Scholar
  10. 10.
    Langen KJ, Roosen N, Coenen HH, Kuikka JT, Kuwert T, Herzog H, Stöcklin G, Feinendegen LE (1991) J Nucl Med 32(6):1225–1229Google Scholar
  11. 11.
    Boado RJ, Li JY, Tsukamoto H, Pardridge WM (2003) J Neurochem 85(4):1037–1042CrossRefGoogle Scholar
  12. 12.
    Soh H, Wasa M, Fukuzawa M (2007) J Pediatr Surg 42(4):608–612CrossRefGoogle Scholar
  13. 13.
    Malik N, Machulla H-J, Solbach C, Winter G, Reske SN, Zlatopolskiy B (2011) Appl Radiat Isot 69(7):1014–1018CrossRefGoogle Scholar

Copyright information

© Akadémiai Kiadó, Budapest, Hungary 2012

Authors and Affiliations

  • Noeen Malik
    • 1
  • Xian Lin
    • 1
  • Dirk Löffler
    • 2
  • Bin Shen
    • 3
  • Christoph Solbach
    • 1
  • Gerald Reischl
    • 4
  • Wolfgang Voelter
    • 5
  • Hans-Jürgen Machulla
    • 1
  1. 1.Klinik für Nuklear MedizinUniversitäts-Klinikum, Ulm UniversitätUlmGermany
  2. 2.Institute of Radiopharmaceutical SciencesEidgenössische Technische HochschuleZürichSwitzerland
  3. 3.Department of RadiologyStanford University Medical CenterStanfordUSA
  4. 4.Department for Preclinical Imaging and Radiopharmacy, University HospitalEberhard Karls UniversityTübingenGermany
  5. 5.Interfacultary Institute for BiochemistryEberhard Karls UniversityTübingenGermany

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