This grant builds upon the research from a prior grant: Developing New 18F-based Brain Tracers for Imaging Nerve Interactions (Synapses) in the Human Brain
Study Rationale:
A synapse is a structure that allow nerve cells (neurons) to communicate with one another or with target cells. In the brain, changes in synaptic density are associated with a variety of brain disorders and psychiatric diseases. The development of tracers for medical imaging by positron emission tomography (PET) scans can enable the diagnosis of degenerative disorders and help test new drugs that target synaptic repair and recovery. One brain tracer (11C-UCB-J) can already detect synaptic changes in people with neurodegenerative diseases, but it has limitations. We aim to develop new and longer lived tracers to image the brains of people with Parkinson’s and other brain diseases.
Hypothesis:
We hypothesize that new tracers radiolabeled with the isotope fluorine-18 will be superior to the known tracer, and this work will lead to widespread use of this PET imaging tool.
Study Design:
Step 1: Create three new 18F‑labeled brain tracers and identify the best-performing tracer of the three by conducting PET scans.
Step 2: Test the top 18F‑labeled brain tracer by assessing the radiation dose and assess toxicity in pre-clinical studies.
Step 3: File regulatory submission to Health Canada and the U.S. Food and Drug Administration to conduct first-in-human studies with the selected top 18F- labeled tracer.
Step 4: Conduct the first-in-human PET studies to test 18F- labeled tracer’s feasibility.
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 test also would make it easier to test the effects of synaptic density as a biomarker of Parkinson’s disease.
Next Steps for Development:
If successful, the probe could be used in clinical research, to directly measure synaptic density in humans. Furthermore, it would help identify a dose for drugs targeting synaptic density to be used in clinical trials.