Electrophilic Addition of Chlorine Monofluoride for PET tracers

We have studied the utility of [F-18]ClF electrophilic addition to the carbon-carbon double bond of analogues of a model positron emission tomography (PET) tracer, [F-18]EF5. The consequence of simultaneous chlorine/fluorine addition on lipophilicity and biological activity of the molecule is evaluated. Post-target produced [F-18]F-2 was reacted with Cl-2 to produce [F-18]ClF, which was used in electrophilic addition. [F-18]ClF was produced and used to label chlorinated analogues of [F-18]EF5. The chlorinated analogues, [F-18]EF4Cl(a) and [F-18]EF4Cl(b), were synthesized simultaneously. The in vivo uptake of the analogues compared well with [F-18]EF5 uptake in tumor-bearing mice. [F-18]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 [F-18]EF5 by monofluorine-for-chlorine exchange affected the lipophilicity, but the hypoxia avidity of these molecules was not apparently altered.