Parkinson's disease results from a decrease in the production of dopamine, a molecule that ensures the transmission of messages from neurons in a specific area of the brain called the substantia nigra to neurons in the frontal cortex or putamen involved in the control of movement. Growing evidence shows that this disease is associated with an inflammatory response in the brain, also referred to as neuroinflammation. However, several questions remain unanswered, such as the precise location of the neuroinflammation in these patients or the relationship between decreased dopamine production and the neuroinflammatory response.
Neuroinflammation can be visualized by positron emission tomography (PET). This imaging technique can monitor the functional activity of neurons and other cell types with weakly radioactive molecules called radiotracers. Among the different radiotracers available, [18F]-DPA714 binds specifically to TSPO, a protein produced in large quantities during the inflammatory response of cells. This particular affinity makes [18F]-DPA714 a preferred radiotracer for monitoring neuroinflammation.
The researchers used PET imaging of the brain with this tracer to study the neuroinflammatory response of a cohort of 25 Parkinson's patients at different stages of the disease. The results reveal in these patients a significant increase in [18F]-DPA714 binding in the substantia nigra, where dopamine-producing neurons degenerate, and in the main regions that receive dopaminergic messages, such as the putamen and frontal cortex.
The detection of a more intense neuroinflammation in these regions particularly affected by the disease confirms what other teams have already observed using other tracers of TSPO and on smaller cohorts of patients.
By providing precise visualization of the increased neuroinflammatory response in the brain of Parkinson's patients, [18F]-DPA714 presents itself as a promising tool to evaluate anti-inflammatory drugs for this disease, and a valuable means to monitor neuroinflammation in other neurodegenerative pathologies.
Increased neuroinflammation in the substantia nigra in a patient with Parkinson's disease compared to a healthy subject. A: Representative MRI showing the outline made at the level of the substantia nigra (right and left) to analyze [18F]-DPA714 binding in this region. B: On the same cross-section, the superposition of the MRI and the [18F]-DPA714 PET image in a healthy subject. There is little binding of the radiotracer in the bilateral substantia nigra region. C: In a subject with Parkinson's disease representative of the study, tracer binding is increased on the most affected side, i.e. on the opposite side to the one presenting clinical symptoms in the patient. © Sonia Lavisse/CEA-Jacob/LMN/MIRCen