Microglial activation in Parkinson's disease using [¹⁸F]-FEPPA.

Area of Science:

• Neuroscience
• Radiochemistry
• Medical Imaging

Background:

• Neuroinflammation, characterized by activated microglia, is implicated in Parkinson's disease (PD).
• Translocator protein (TSPO) expression increases with brain injury and neurodegeneration.
• Positron emission tomography (PET) targeting TSPO enables in vivo quantification of neuroinflammation.

Purpose of the Study:

• To evaluate regional differences in [18F]-FEPPA binding between PD patients and healthy controls (HC).
• To assess the influence of TSPO gene rs6971 polymorphism on [18F]-FEPPA binding in PD and HC.

Main Methods:

• Inclusion of 25 mixed-affinity binders (MABs) and 27 high-affinity binders (HABs) based on rs6971 genotype.
• PET imaging with the TSPO-targeting radioligand [18F]-FEPPA.
• Quantification of total distribution volume (V_T) using a two-tissue compartment model with arterial input.

Main Results:

• A significant main effect of TSPO genotype on [18F]-FEPPA V_T was observed across all brain regions.
• No significant main effect of PD or disease × genotype interaction on [18F]-FEPPA V_T was found.
• Mean [18F]-FEPPA V_T differences between MABs and HABs were 32.6% in HC and 43.1% in PD patients.

Conclusions:

• TSPO genotype significantly influences [18F]-FEPPA binding, irrespective of Parkinson's disease status.
• Further research is required to establish [18F]-FEPPA as a reliable neuroinflammation biomarker in PD.
• The clinical significance of the rs6971 polymorphism in PD warrants additional investigation.