Electrophilic addition of chlorine monofluoride for PET tracers.

Abstract

PURPOSE:

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

PROCEDURES:

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

RESULTS:

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

CONCLUSION:

[(18)F]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 [(18)F]EF5 by monofluorine-for-chlorine exchange affected the lipophilicity, but the hypoxia avidity of these molecules was not apparently altered.

• Authors: Anna Kirjavainen, Sarita Forsback, Tove J Grönroos, Laura Haavisto, Merja Haaparanta, Olof Solin
• Journal: Molecular imaging and biology (Mol Imaging Biol) Vol. 15 Issue 2 Pg. 131-5 (Apr 2013) ISSN: 1860-2002 [Electronic] United States
• PMID: 22869463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chlorides
• Hydrocarbons, Fluorinated
• Radiopharmaceuticals
• Etanidazole
• 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide
• Fluorides

Topics

• Animals
• Chlorides (chemistry, pharmacokinetics)
• Etanidazole (analogs & derivatives, chemistry, pharmacokinetics)
• Fluorides (chemistry, pharmacokinetics)
• Hydrocarbons, Fluorinated (chemistry, pharmacokinetics)
• Male
• Mice
• Mice, Nude
• Neoplasms, Experimental (diagnostic imaging, metabolism)
• Positron-Emission Tomography (methods)
• Radiopharmaceuticals (chemical synthesis, chemistry, pharmacokinetics)