Development of a Colony Stimulating Factor 1 Receptor (CSF1R) Radioligand for Imaging Microglia-selective Inflammation

Study Rationale:
We have shown that Parkinson’s disease has an underlying neuroinflammatory component that involves microglia, which are inflammatory and immune cells in the brain. We have developed an imaging agent that uses positron emission tomography (PET) that can detect microglia specifically. We propose that our imaging agent, [¹¹C]CPPC, will be a new biomarker tool for detecting and measuring neuroinflammation associated with Parkinson’s disease and can be used to select patients for appropriate therapies, for drug development and for determining prognosis.

Hypothesis:
We seek to determine if [¹¹C]CPPC brain PET can distinguish individuals with Parkinson’s disease from healthy, matched control vounteers.

Study Design:
We have two aims. The first will use post-mortem human tissues from individuals who had pathologically proven Parkinson’s disease and will probe them for binding of [¹¹C]CPPC using autoradiography. If that aim proves that we can distinguish tissue from patients with Parkinson’s disease from tissue from control volunteers, we will move to live human brain PET imaging with [¹¹C]CPPC. In both aims the goal is to find a significant difference between patients with Parkinson’s disease and healthy individuals. 

Impact on Diagnosis/Treatment of Parkinson’s Disease:
[¹¹C]CPPC brain PET will provide an entirely new way to detect and measure aspects of Parkinson’s disease, namely neuroinflammation, directly, non-invasively and repeatedly, as needed.

Next Steps for Development:
This project is a clinical study using only human tissues (Aim 1) or living subjects (Aim 2). [¹¹C]CPPC has been licensed to a Johns Hopkins start-up company, Precision Molecular, and will be commercialized if this trial is successful.

Trial Phase: Aim 2 is a Phase 1 trial.