18F-OP-801 (18F Hydroxyl Dendrimer) is an experimental PET (Positron Emission Tomography) imaging agent developed by Ashvattha Therapeutics for detecting neuroinflammation in the brain. This Phase 1/2 clinical trial evaluates the safety, biodistribution, and imaging characteristics of this novel radiotracer in participants with Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and healthy volunteers[1][2].
The key innovation of 18F-OP-801 is its selective uptake by activated microglia while sparing resting microglia, offering the potential to detect neuroinflammation at lower levels and earlier stages of neurodegenerative diseases. This represents a significant advancement over existing PET tracers for neuroinflammation, which generally cannot differentiate between microglial activation states[3].
| Attribute | Value |
|---|---|
| Trial Name | 18F-OP-801 Phase 1/2 |
| NCT Number | NCT05395624 |
| Phase | Phase 1/2 |
| Status | RECRUITING |
| Enrollment | 65 participants (estimated) |
| Start Date | 2022 |
| Locations | UCSF (San Francisco), Stanford University (Stanford), Mayo Clinic Jacksonville (Jacksonville, FL) |
Neuroinflammation is a hallmark of multiple neurodegenerative diseases, driven primarily by activated microglia—the brain's resident immune cells. In Alzheimer's disease, Parkinson's disease, ALS, and MS, neuroinflammation contributes to disease progression through:
18F-OP-801 is a hydroxyl dendrimer-based PET radiotracer designed to selectively bind to activated microglia and macrophages in the brain. The molecular targeting mechanism involves:
| Feature | 18F-OP-801 | TSPO Tracers (e.g., PK11195) |
|---|---|---|
| Target | Activated microglia | TSPO (all microglia) |
| Specificity | High (activated only) | Moderate ( TSPO expressed in multiple cell types) |
| Signal-to-noise | Potentially higher | Variable |
| Early detection | Yes - lower threshold | Limited |
| Resting microglia signal | Minimal | Present |
Primary Endpoint: Number of participants with treatment-emergent adverse events (TEAEs) from Day 1 to Day 15/18-29.
Safety assessment includes:
The trial monitors for any acute reactions to the radiotracer administration, as 18F-OP-801 is administered intravenously at very low mass doses typical of PET radiotracers.
Ability to detect neuroinflammation - PET signal intensity in regions of known neuroinflammation in:
Test/retest imaging repeatability - Reliability of the imaging signal on repeated administration
Plasma NfL correlation - Relationship between plasma neurofilament light chain (NfL) levels and 18F-OP-801 uptake in brain regions
Clinical scale correlations - Correlation between PET signal and clinical measures:
Neuroinflammation is both a consequence and a driver of neurodegeneration. In Alzheimer's disease, microglial activation correlates with amyloid deposition and precedes clinical symptoms. In Parkinson's disease, neuroinflammation accompanies alpha-synuclein pathology. In ALS, microglial activation is prominent throughout disease progression.
The ability to visualize and quantify neuroinflammation in vivo provides:
Current neuroinflammation PET tracers target the 18 kDa translocator protein (TSPO), which is expressed in both activated and resting microglia, as well as in other cell types. This limitation leads to:
18F-OP-801 addresses these limitations by targeting a more specific marker of activated microglia, potentially enabling earlier detection and more accurate quantification of neuroinflammation.
The development of 18F-OP-801 as a neuroinflammation biomarker enables:
Successful development of 18F-OP-801 could support: