Study Rationale: Parkinson´s disease (PD) is associated with neuroinflammation and the activation of microglia, cells that belong to the brain’s immune system. A protein called Colony stimulating factor 1 receptor (CSF1R) is present on the surface of microglia and is directly involved in their survival, development and function. Positron emission tomography (PET) is an imaging technology that uses compounds labeled with radioactive carbon (carbon-11) or fluorine (fluorine-18) to study the brain. Imaging of CSF1R with PET could provide a valuable tool for studying neuroinflammation in PD and assessing how it changes during disease progression and in response to treatment.
Hypothesis: We hypothesize that selective CSF1R compounds that enter the brain and are amenable to labeling with fluorine-18 or carbon-11 will be suitable tools for noninvasive brain PET studies of inflammation in animal models and people with PD.
Study Design: We will develop a series of novel compounds and characterize how well they bind to CSF1R and to other, unwanted target proteins. We will also ensure that these compounds can reach the brain and that they can be radiolabeled for use as PET tracers. Through trials using brain tissue and animal models, we will test the selectivity and specificity of the CSF1R-binding compounds we develop.
Impact on Diagnosis/Treatment of Parkinson’s disease: Development of a brain-penetrant PET tracer for detecting CSF1R would support diagnosis of PD prior to symptom onset or in early stages. It will also allow the monitoring of changes in CSF1R associated with disease progression and treatment effects.
Next Steps for Development: If we successfully identify a compound that binds to CSF1R and fulfills our criteria for a brain-penetrant PET radioligand, the next step would be to continue its development for use in studies of people with PD.