This Phase 1/2 clinical trial conducted at the University of Alabama at Birmingham (UAB) uses TSPO PET imaging to study neuroinflammation in Parkinson's disease. The trial investigates the role of translocator protein (TSPO) as a biomarker for microglial activation and neuroinflammatory processes in PD.
| Field | Value |
|---|---|
| Trial ID | NCT03457493 |
| Phase | Phase 1/2 |
| Status | Completed |
| Institution | University of Alabama at Birmingham |
| Imaging Agent | TSPO PET tracer |
| Target | Microglial activation/neuroinflammation |
Neuroinflammation is a central pathological feature of Parkinson's disease, involving both the central nervous system (CNS) and peripheral immune systems. The inflammatory response in PD is complex and involves multiple cell types and signaling pathways.
| Cell Type | Role in PD | Activation Markers |
|---|---|---|
| Microglia | CNS immune surveillance | TSPO, CD68, Iba1 |
| Astrocytes | Neuroprotective/glial scar | GFAP, S100B |
| T cells | Peripheral infiltration | CD3, CD4, CD8 |
| B cells | Humoral immunity | CD19, CD20 |
| Peripheral monocytes | Blood-brain barrier crossing | CD14, CD16 |
Microglia can adopt different activation states:
M1 (Pro-inflammatory):
M2 (Anti-inflammatory):
| Disease Stage | Inflammatory Activity |
|---|---|
| Prodromal | Low-grade chronic inflammation |
| Early PD | Active microglial activation |
| Mid-stage PD | Peak inflammatory response |
| Advanced PD | Burned-out inflammation, neuronal loss |
Translocator protein (TSPO), formerly known as the peripheral benzodiazepine receptor, is a mitochondrial protein located primarily on the outer mitochondrial membrane. Key characteristics:
| Condition | TSPO Expression | PET Signal |
|---|---|---|
| Healthy brain | Low baseline | Low |
| Alzheimer's disease | Elevated | Increased |
| Parkinson's disease | Elevated | Increased |
| Multiple sclerosis | Highly elevated | Very high |
| Stroke | Regionally elevated | Variable |
Multiple TSPO PET tracers have been developed:
| Tracer | Affinity | Selectivity | Limitations |
|---|---|---|---|
| [11C]PK11195 | High | Good | Short half-life, nonspecific binding |
| [11C]PBR28 | High | Moderate | Genetic polymorphism (Ala147Thr) |
| [18F]FEPPA | High | Good | Metabolite issues |
| [18F]DPA-714 | High | Excellent | Optimal imaging time |
| [11C]ABP688 | Moderate | Excellent | Low signal in disease |
The trial employs TSPO-binding PET radiotracers to visualize and quantify microglial activation in vivo:
| Metric | Description | Clinical Use |
|---|---|---|
| BPND | Binding potential (non-displaceable) | Target engagement |
| SUVR | Standardized uptake value ratio | Relative binding |
| VT | Distribution volume | Absolute measure |
| Distribution pattern | Regional involvement | Disease staging |
Primary Objectives:
Secondary Objectives:
| Group | Characteristics |
|---|---|
| Early PD | Disease duration <5 years, Hoehn-Yahr 1-2.5 |
| Mid-stage PD | Disease duration 5-10 years |
| Healthy controls | Age-matched, neurologically normal |
| Patients with atypical parkinsonism | For comparison |
| Assessment | Scale | Domain |
|---|---|---|
| Motor examination | MDS-UPDRS Part III | Motor function |
| Daily activities | MDS-UPDRS Part II | Functional status |
| Cognitive function | MoCA, MMSE | Cognition |
| Non-motor symptoms | NMSS | Non-motor burden |
| Quality of life | PDQ-39 | Overall wellbeing |
Based on prior literature, TSPO PET in PD typically shows:
This biomarker study may:
Understanding neuroinflammation enables:
Anti-inflammatory drug development:
Treatment stratification:
Outcome prediction: