18F-OP-801 Ashvattha Neuroinflammation PET Imaging Trial
Overview
flowchart TD
clinical_trials_18f_op_801_ash["18F-OP-801 Ashvattha Neuroinflammation PET Imagi"]
clinical_trials_18f_op_801_ash["OP-801"]
clinical_trials_18f_op_801_ash -->|"related to"| clinical_trials_18f_op_801_ash
style clinical_trials_18f_op_801_ash fill:#81c784,stroke:#333,color:#000
clinical_trials_18f_op_801_ash["Imaging"]
clinical_trials_18f_op_801_ash -->|"related to"| clinical_trials_18f_op_801_ash
style clinical_trials_18f_op_801_ash fill:#81c784,stroke:#333,color:#000
clinical_trials_18f_op_801_ash["Trial"]
clinical_trials_18f_op_801_ash -->|"related to"| clinical_trials_18f_op_801_ash
style clinical_trials_18f_op_801_ash fill:#81c784,stroke:#333,color:#000
clinical_trials_18f_op_801_ash["Hydroxyl"]
clinical_trials_18f_op_801_ash -->|"related to"| clinical_trials_18f_op_801_ash
style clinical_trials_18f_op_801_ash fill:#81c784,stroke:#333,color:#000
style clinical_trials_18f_op_801_ash fill:#4fc3f7,stroke:#333,color:#000
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["@clinicaltrials2022"][@ashvattha2024].
...18F-OP-801 Ashvattha Neuroinflammation PET Imaging Trial
Overview
Mermaid diagram (expand to render)
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["@clinicaltrials2022"][@ashvattha2024].
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["@tournier2022"].
Trial Details
| 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) |
- Lead Sponsor: Ashvattha Therapeutics, Inc.
- Collaborators: UCSF, Stanford University, Mayo Clinic
Study Design
- Allocation: Non-randomized (imaging study)
- Intervention Model: Single group
- Masking: None (open-label imaging)
- Primary Purpose: Diagnostic (imaging biomarker)
Mechanism of Action
Neuroinflammation in Neurodegenerative Diseases
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:
- Cytokine release: Pro-inflammatory cytokines (IL-1β, TNF-α, IL-6) that damage neurons
- Oxidative stress: Reactive oxygen species that cause lipid peroxidation and DNA damage
- Excitotoxicity: Dysregulated glutamate signaling leading to calcium overload
- Protein aggregation: Enhanced aggregation of amyloid-beta, alpha-synuclein, and tau
- Synaptic dysfunction: Loss of synaptic connections and neuronal communication
18F-OP-801: Activated Microglia Targeting
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:
Dendrimer Structure: The hydroxyl-terminated dendrimer provides a highly branched scaffold that can be radiolabeled with fluorine-18
Microglial Specificity: The tracer is selectively taken up only by activated (not resting) microglia, offering superior specificity compared to existing TSPO-based tracers
Blood-Brain Barrier Penetration: Designed to cross the blood-brain barrier and reach target regions
Quantitative PET Signal: Provides quantitative biological information in vivo at very low radiotracer doses without pharmacological effectsAdvantages Over Existing Neuroinflammation Tracers
| 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 Outcomes
Safety and Tolerability
Primary Endpoint: Number of participants with treatment-emergent adverse events (TEAEs) from Day 1 to Day 15/18-29.
Safety assessment includes:
- Physical examinations
- Vital signs monitoring
- Laboratory tests (hematology, chemistry)
- ECG monitoring
- Adverse event recording
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.
Secondary Outcomes
Biodistribution
Whole body PET/MRI or PET/CT scans - Assessment of tracer distribution across organ systems
Clearance measurement - Pharmacokinetics of 18F-OP-801 elimination from the body
Time-activity curves - Quantitative analysis of tracer uptake over timeNeuroinflammation Imaging
Ability to detect neuroinflammation - PET signal intensity in regions of known neuroinflammation in:
- Alzheimer's disease participants
- Parkinson's disease participants
- ALS participants
- MS participants
- Healthy volunteers (control)
Test/retest imaging repeatability - Reliability of the imaging signal on repeated administrationBiomarker Correlations
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:
- ALS: ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) / PUMNS (Progressive Upper Motor Neuron Scale)
- Alzheimer's: MMSE (Mini-Mental State Examination)
- MS: EDSS (Expanded Disability Status Scale)
- Parkinson's: SE-ADL (Schwab and England Activities of Daily Living)
Scientific Rationale
Why Detect Neuroinflammation?
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:
Diagnostic value: Earlier and more accurate diagnosis
Progression monitoring: Tracking disease advancement
Therapeutic target engagement: Measuring drug effects on inflammation
Patient stratification: Identifying patients with high neuroinflammation
Clinical trial enrichment: Selecting patients likely to respond to anti-inflammatory therapiesThe Need for Better Tracers
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:
- Lower signal-to-noise ratios
- Inability to detect early/lower-level inflammation
- Variable binding due to TSPO polymorphisms
- Poor specificity for disease-specific neuroinflammation
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.
Clinical Sites
UCSF (University of California, San Francisco)
- Leading neuroscience research center
- Active neuroimaging program for neurodegenerative diseases
- Experienced in PET imaging clinical trials
Stanford University (Stanford, CA)
- Center for neurodegenerative disease research
- Advanced PET/MRI imaging capabilities
- Collaborative neuroscience programs
Mayo Clinic Jacksonville (Jacksonville, FL)
- Comprehensive neurodegenerative disease program
- Clinical trial expertise
- PET imaging infrastructure
Future Directions
Therapeutic Development Implications
The development of 18F-OP-801 as a neuroinflammation biomarker enables:
Anti-inflammatory therapy development - Clinical trials can now measure target engagement of anti-inflammatory drugs
Patient selection - Identifying patients with elevated neuroinflammation for targeted therapies
Combination therapy monitoring - Assessing effects of disease-modifying therapies on neuroinflammationExpansion Potential
Successful development of 18F-OP-801 could support:
- Phase 3 registration trials
- Companion diagnostic development
- Expansion to additional neurodegenerative indications
- Use in clinical practice for diagnosis and monitoring
Related Pages
- [Neuroinflammation Overview](/mechanisms/neuroinflammation)
- [Microglia in Neurodegeneration](/cell-types/microglia)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Amyotrophic Lateral Sclerosis (ALS)](/diseases/als)
- [Multiple Sclerosis](/diseases/multiple-sclerosis)
- [PET Imaging in Neurodegeneration](/diagnostics/pet-imaging-neurodegeneration)
- [Neuroinflammation Biomarkers](/biomarkers/neuroinflammation-biomarkers)
- [Ashvattha Therapeutics](/organizations/ashvattha-therapeutics)
References
[Ashvattha Therapeutics Corporate Overview (2024)](https://www.ashvatthatherapeutics.com/)
[18F-OP-801 PET Imaging for Neuroinflammation NCT05395624](https://clinicaltrials.gov/study/NCT05395624)
[Kumar et al., PET imaging of neuroinflammation in neurodegenerative diseases (2023)](https://doi.org/10.1038/s41582-023-00756-8)
[Tournier et al., 18F-OP-801: A novel PET tracer for activated microglia (2022)](https://doi.org/10.1186/s43514-022-00067-8)