Synthesis and murine tissue uptake of sodium [18F]fluoroacetate

Area of Science:

• Biochemistry
• Radiochemistry
• Pharmacokinetics

Background:

• Fluoroacetate (FAc) is a potent biochemical agent and rodenticide (1080).
• Its in vivo behavior and metabolic fate remain poorly understood.
• Understanding FAc's distribution is crucial for assessing its toxicity and potential applications.

Purpose of the Study:

• To synthesize fluorine-18 labeled fluoroacetate ([18F]FAc) for in vivo studies.
• To investigate the biodistribution and pharmacokinetic profile of [18F]FAc in mice.
• To identify potential sites of defluorination in vivo.

Main Methods:

• Radiolabeling of FAc using a heat-assisted halogen exchange reaction with [18F]fluoride.
• Synthesis involved converting radiofluorine gas to [18F]tetrabutylammonium fluoride.
• Purification and hydrolysis of the ester precursor to yield [18F]FAc.
• Biodistribution studies in mice over a 4-hour period.

Main Results:

• [18F]FAc was synthesized in 30% yield.
• Preliminary studies in mice showed low retention in soft tissues over 4 hours.
• Significant accumulation of radioactivity was observed in bone, indicating defluorination.

Conclusions:

• The developed method allows for the synthesis of [18F]FAc.
• [18F]FAc exhibits limited soft tissue distribution but significant bone uptake in mice.
• Bone accumulation suggests in vivo defluorination of fluoroacetate.