Synthesis of two novel [

Area of Science:

• Radiochemistry
• Neuroimaging
• Molecular Imaging

Background:

• Translocator protein (18 kDa) (TSPO) is a key biomarker in neuroinflammation.
• Developing effective positron emission tomography (PET) radiotracers is crucial for visualizing TSPO in brain conditions.

Purpose of the Study:

• To synthesize and evaluate two novel [18F]-labeled radiotracers, [18F]5 and [18F]6, for PET imaging of TSPO in ischemic brain.
• To assess their in vitro and in vivo characteristics, including binding affinity, stability, and performance in preclinical models.

Main Methods:

• Synthesis of [18F]5 and [18F]6 via radiofluorination of spirocyclic iodonium ylide precursors.
• In vitro binding assays to determine affinity for TSPO.
• In vivo evaluation in mice and rats, including metabolite analysis and PET imaging of ischemic brain.

Main Results:

• [18F]5 and [18F]6 were successfully synthesized with good radiochemical yields.
• [18F]5 exhibited high TSPO binding affinity (Ki = 0.70 nM) and improved in vivo stability compared to parent tracers.
• PET imaging with [18F]5 in ischemic rats showed high binding potential (BPND = 3.42) and specific uptake in the affected brain region.

Conclusions:

• [18F]5 is a highly effective PET radiotracer for visualizing TSPO in neuroinflammation models.
• The developed radiotracers offer potential for improved diagnosis and monitoring of neurological disorders involving neuroinflammation.