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Electrophilic Addition of Chlorine Monofluoride for PET tracers

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Abstract

Purpose

We have studied the utility of [18F]ClF electrophilic addition to the carbon–carbon double bond of analogues of a model positron emission tomography (PET) tracer, [18F]EF5. The consequence of simultaneous chlorine/fluorine addition on lipophilicity and biological activity of the molecule is evaluated.

Procedures

Post-target produced [18F]F2 was reacted with Cl2 to produce [18F]ClF, which was used in electrophilic addition.

Results

[18F]ClF was produced and used to label chlorinated analogues of [18F]EF5. The chlorinated analogues, [18F]EF4Cla and [18F]EF4Clb, were synthesized simultaneously. The in vivo uptake of the analogues compared well with [18F]EF5 uptake in tumor-bearing mice.

Conclusion

[18F]ClF is a suitable labeling reagent for electrophilic addition to double bonds of PET tracers. The results show that the modification of the pentafluoro group of [18F]EF5 by monofluorine-for-chlorine exchange affected the lipophilicity, but the hypoxia avidity of these molecules was not apparently altered.

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References

  1. Welch MJ, Redvanly CS (eds) (2003) Handbook of radiopharmaceuticals. Wiley, Chichester

    Google Scholar 

  2. Ametamey SM, Honer M, Schubiger PA (2008) Molecular imaging with PET. Chem Rev 108:1501–1516

    Article  PubMed  CAS  Google Scholar 

  3. Chambers RD (2004) Fluorine in organic chemistry. Blackwell, Oxford

    Book  Google Scholar 

  4. Blessing G, Coenen HH, Franken K, Qaim SM (1986) Production of [18F]F2, H18F and 18Faq using the 20Ne(d, α)18F process. Appl Radiat Isot 37:1135–1139

    Article  CAS  Google Scholar 

  5. Harris A (2002) Hypoxia—a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47

    Article  PubMed  CAS  Google Scholar 

  6. Vaupel P (2008) Hypoxia and aggressive tumor phenotype: implications for therapy and prognosis. Oncologist 13:21–26

    Article  PubMed  CAS  Google Scholar 

  7. Grönroos T, Eskola O, Lehtiö K et al (2001) Pharmacokinetics of [18F]FETNIM: a potential hypoxia marker for PET. J Nucl Med 42:1397–1404

    PubMed  Google Scholar 

  8. Mees G, Dierckx R, Vangestel C, Van de Wiele C (2009) Molecular imaging of hypoxia with radiolabelled agents. Eur J Nucl Med Mol Imaging 36:1674–1686

    Article  PubMed  CAS  Google Scholar 

  9. Minn H, Grönroos TJ, Komar G et al (2008) Imaging of tumor hypoxia to predict treatment sensitivity. Curr Pharm Design 14:2932–2942

    Article  CAS  Google Scholar 

  10. Komar G, Seppänen M, Eskola O et al (2008) A new PET tracer for imaging hypoxia in head and neck cancer. J Nucl Med 49:1944–1951

    Article  PubMed  Google Scholar 

  11. Bergman J, Solin O (1997) Fluorine-18-Labeled fluorine gas for synthesis of tracer molecules. Nucl Med Biol 24:677–683

    Article  PubMed  CAS  Google Scholar 

  12. OECD Guideline for the testing of chemicals, partition coefficient (n-octanol/water): shake method, adopted by the Council on 1995, Test no. 107, ISSN: 2074-5753, (online). doi: 10.1787/20745753

  13. Jeschke P (2010) The unique role of halogen substituents in the design of modern agrochemicals. Pest Manag Sci 66:10–27

    Article  PubMed  CAS  Google Scholar 

  14. Koch CJ, Hahn SM, Rockwell K, Covey JM, McKenna WG, Evans SM (2001) Pharmacokinetics of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide] in human patients: implications for hypoxia measurements in vivo by 2-nitroimidazoles. Cancer Chemother Pharmacol 48:177–187

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The precursor and reference compounds were gifts from Prof. Cameron J. Koch, PhD, University of Pennsylvania, Philadelphia, PA, USA. Adenocarcinoma cell lines were from Dr. Cecilia Sahlgren, PhD, Turku Centre for Biotechnology, Åbo Akademi University, and University of Turku, Turku, Finland. This study was funded by the Academy of Finland (project number 116084) and the Finnish Centre of Excellence in Molecular Imaging in Cardiovascular and Metabolic Research.

Conflict of Interest

The authors declare no conflict of interest in this work.

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Correspondence to Olof Solin.

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Kirjavainen, A., Forsback, S., Grönroos, T.J. et al. Electrophilic Addition of Chlorine Monofluoride for PET tracers. Mol Imaging Biol 15, 131–135 (2013). https://doi.org/10.1007/s11307-012-0584-9

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  • DOI: https://doi.org/10.1007/s11307-012-0584-9

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