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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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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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