Study Rationale:
A synapse is a structure that allow nerve cells (i.e., neurons) to communicate with one-another or with target cells. Changes in synaptic density are associated with a variety of brain disorders and psychiatric diseases, including Parkinson's and Alzheimer's. An imaging agent that detects synaptic changes could be used to diagnose brain diseases and determine patient response to therapies targeting synapses. One brain tracer (11C-UCB-J) can already detect synaptic changes in patients with such diseases but has limitations. In this project, we will develop new, longer lasting brain imaging tracers for positron emission tomography (PET) as a diagnostic and response biomarker for patients with Parkinson's disease and several other brain disorders.
Hypothesis:
We hypothesize that the new brain tracers radiolabeled with the isotope fluorine-18 will be superior to the known brain tracer, and this work will lead to widespread use of this PET imaging scan for diagnosis and measuring therapeutic response in brain diseases.
Study Design:
We will begin by creating three new 18F labeled brain tracers. We will then identify the best-performing tracer of the three by conducting positron emission tomography (PET) scans. The next step is to test the best-performing 18F labeled brain tracer by assessing the radiation dose and toxicity in preclinical studies. Once the preclinical testing is complete, we will file regulatory submission to Health Canada and U.S. FDA to conduct first-in-human studies with the selected top 18F- labeled tracer. If the submission is approved, we will move to conduct first-in-human PET studies to test the 18F- labeled tracer's feasibility as a diagnostic and response marker for brain diseases.
Impact on Diagnosis/Treatment of Parkinson's disease:
With an imaging agent to accurately test how well drug candidates impact synaptic density, researchers will better be able to select which ones should be tested in humans and at what doses. This imaging agent would also help determine whether synaptic density is a useful biomarker in Parkinson's disease.
Next Steps for Development:
If these studies are successful, the tracer could be used in clinical research to directly measure synaptic density in humans. Furthermore, it could help identify a dose for therapeutics targeting synaptic density to be used in clinical trials for Parkinson's disease.