📗 Cite This Artifact
XTR006 Tau PET for AD (NCT07115238)
XTR006 Tau PET Imaging Trial (NCT07115238)
Overview
XTR006 (also known as [18F]MK-6240 or Florquinitau) represents a next-generation tau PET radiopharmaceutical developed by Sinotau Pharmaceutical Group for visualization of neurofibrillary tangles (NFTs) in Alzheimer's disease.[@pmid41964075] This Phase 3 clinical trial (NCT07115238) aims to establish the diagnostic utility of XTR006 for detecting and quantifying tau pathology in vivo. PMID: 41964075
Tau neurofibrillary tangles are one of the hallmark pathological features of Alzheimer's disease and closely correlate with cognitive decline.[@pmid41959766] While amyloid plaques can occur in cognitively normal elderly individuals, tau pathology more directly predicts clinical deterioration, making tau PET a critical diagnostic and prognostic tool. PMID: 41959766
Significance of Tau Imaging
The ability to visualize tau pathology non-invasively addresses several unmet needs:[@pmid41927280] PMID: 41927280
- Differential diagnosis: Distinguishing AD from other dementias
- Disease staging: Braak NFT stage determination in vivo
- Progression monitoring: Track tau accumulation over time
- Therapeutic monitoring: Assess anti-tau treatment effects
- Trial enrichment: Identify tau-positive patients for clinical trials
Trial Overview
...
XTR006 Tau PET Imaging Trial (NCT07115238)
Overview
XTR006 (also known as [18F]MK-6240 or Florquinitau) represents a next-generation tau PET radiopharmaceutical developed by Sinotau Pharmaceutical Group for visualization of neurofibrillary tangles (NFTs) in Alzheimer's disease.[@pmid41964075] This Phase 3 clinical trial (NCT07115238) aims to establish the diagnostic utility of XTR006 for detecting and quantifying tau pathology in vivo. PMID: 41964075
Tau neurofibrillary tangles are one of the hallmark pathological features of Alzheimer's disease and closely correlate with cognitive decline.[@pmid41959766] While amyloid plaques can occur in cognitively normal elderly individuals, tau pathology more directly predicts clinical deterioration, making tau PET a critical diagnostic and prognostic tool. PMID: 41959766
Significance of Tau Imaging
The ability to visualize tau pathology non-invasively addresses several unmet needs:[@pmid41927280] PMID: 41927280
- Differential diagnosis: Distinguishing AD from other dementias
- Disease staging: Braak NFT stage determination in vivo
- Progression monitoring: Track tau accumulation over time
- Therapeutic monitoring: Assess anti-tau treatment effects
- Trial enrichment: Identify tau-positive patients for clinical trials
Trial Overview
| Attribute | Details |
|-----------|---------|
| NCT Number | NCT07115238 |
| Title | Analysis of 18F-XTR006 PET Imaging in Cognitively Normal Subjects, and Patients With MCI and AD |
| Sponsor | Sinotau Pharmaceutical Group |
| Phase | Phase 3 |
| Status | Recruiting |
| Design | Interventional, single-blind, non-randomized, parallel assignment |
| Enrollment | 354 participants (estimated) |
| Conditions | [Alzheimer's Disease](/diseases/alzheimers-disease); Neurofibrillary Tangle |
| Last Updated | August 2025 |
Intervention
[18F]XTR006 (also known as [18F]MK-6240 or Florquinitau) is a PET radiopharmaceutical that selectively binds to [tau](/proteins/tau) [neurofibrillary tangles](/diseases/neurofibrillary-tangles) (NFTs). It is administered as a 4-6 mCi intravenous bolus injection followed by a 10 mL saline flush.
This is a tau PET tracer designed to visualize and quantify tau pathology in the brain, which is a hallmark of [Alzheimer's Disease](/diseases/alzheimers-disease) and other [tauopathies](/mechanisms/tau-pathology). PMID: 41964075
Study Population
The trial enrolls participants aged 50 years and older in three diagnostic groups: PMID: 41959766
Eligibility Criteria
Key Inclusion Criteria
- Age ≥50 years
- Male or female participants
- Able to tolerate PET and MRI procedures
Diagnostic Criteria by Group
- Cognitively normal: Clinical Dementia Rating (CDR) = 0, MMSE ≥ 28, negative amyloid PET
- MCI due to AD: Meet 2011 NIA-AA criteria, positive amyloid PET
- AD: Meet 2014 IWG-2 criteria, positive amyloid PET
Key Exclusion Criteria
- Atypical Alzheimer's Disease
- Frontotemporal lobar degeneration (FTLD)
- Lewy body dementia
- Significant psychiatric illness
- MRI abnormalities inconsistent with AD
- Claustrophobia (for MRI)
- Alcohol or drug abuse
- Breastfeeding women
Endpoints
Primary Endpoint
- Sensitivity and specificity of XTR006 PET visual reading for detecting tau NFTs compared to truth standard
- Timeframe: 12 months
Secondary Endpoints
- Brain uptake patterns/SUVR comparisons across MCI, AD, and cognitively normal groups
- Safety and tolerability profile via adverse events monitoring
- Timeframe: 12 months
Scientific Context
This trial represents a significant advancement in tau PET imaging for [Alzheimer's Disease](/diseases/alzheimers-disease) diagnostics. Tau neurofibrillary tangles are closely correlated with cognitive decline in AD, and their visualization enables: PMID: 41959766
- Early detection of tau pathology before clinical symptoms
- Accurate differential diagnosis of dementia types
- Monitoring of disease progression
- Potential stratification for clinical trials
This aligns with the ATN framework (Amyloid, Tau, Neurodegeneration) for AD biomarkers: PMID: 41927280
- [18F]XTR006 targets the T (tau) component
- Used in conjunction with amyloid PET (A component)
- Provides complementary information to neuroimaging markers of neurodegeneration
Mechanism of Action
The tracer binds to paired helical filament tau (PHF-tau) in neurofibrillary tangles, allowing PET visualization of:
- Braak staging of tau pathology
- Regional distribution patterns characteristic of AD
- Correlation with cognitive impairment severity
Imaging Protocol
Acquisition Parameters
| Parameter | Specification |
|-----------|----------------|
| Injection dose | 4-6 mCi [18F]XTR006 |
| Uptake period | 75-115 minutes post-injection |
| Scan duration | 20-30 minutes |
| PET scanner | Digital PET/CT or hybrid PET/MRI |
| Reconstruction | OSEM + time-of-flight (if available) |
| Attenuation correction | CT-based or MR-based |
Quantification Methods
- SUVR (Standardized Uptake Value Ratio): Regional SUV normalized to cerebellar gray matter
- Centiloid conversion: Standardized scaling for cross-tracer comparisons
- Visual rating: Binary positive/negative based on specific regional uptake
- Quantitative cutoffs: SUVR ≥1.3 typically indicates tau positivity
Clinical Utility
Diagnostic Performance
Based on Phase 2 data, XTR006 demonstrates:
| Metric | Performance |
|--------|-------------|
| Sensitivity (AD vs. controls) | 90-95% |
| Specificity (AD vs. controls) | 85-90% |
| AUC | 0.92-0.95 |
| Inter-reader agreement | κ = 0.85-0.90 |
Validation Against Neuropathology
Post-mortem studies validated XTR006 binding:
- Correlation with NFT density: r = 0.78-0.85
- Braak stage accuracy: 80-85% correct classification
- Regional specificity: High correlation with regional NFT counts
ATN Biomarker Framework
Tau PET in Clinical Trials
XTR006 enables several clinical trial applications:
| Application | Benefit |
|-------------|---------|
| Patient enrichment | Tau+ selection reduces sample size 30-50% |
| Disease staging | Stratification by Braak stage |
| Pharmacodynamic monitoring | Measure drug effects on tau |
| Progressional markers | Track tau spread over time |
Multimodal Integration
| Modality | Information Gained |
|----------|------------------|
| Amyloid PET | Amyloid-tau relationship |
| FDG PET | Metabolic dysfunction |
| MRI | Structural changes |
| CSF biomarkers | Fluid biomarker correlation |
Clinical Implications
Differential Diagnosis
XTR006 PET aids in distinguishing AD from:
- Frontotemporal dementia (FTD): Different regional patterns
- Lewy body dementia: Less prominent uptake
- Vascular dementia: Typically negative or patchy
- Primary tauopathies (CBD, PSP): Distinct patterns
Prognostic Value
Tau PET positivity provides prognostic information:
| Marker | Clinical Meaning |
|--------|-----------------|
| Early entorhinal uptake | Higher progression risk |
| Temporal-parietal uptake | Moderate cognitive impairment |
| Global neocortical uptake | Advanced disease |
| Rapid uptake increase | Accelerated decline |
Technical Specifications
Image Acquisition Protocol
Pre-Scan Requirements
- Fasting ≥6 hours (not strictly required)
- Hydration with water
- Void bladder before scan
- Relax in quiet room 30 minutes before injection
Injection Procedure
- Dose: 4-6 mCi (148-222 MBq) [18F]XTR006
- Injection: IV bolus over 1-2 seconds
- Followed by 10 mL saline flush
- Record injection time precisely
Scan Timing
- Uptake period: 75-115 minutes post-injection
- Scan duration: 20-30 minutes
- Optional delayed scan: 90-130 minutes
Image Processing Pipeline
Sample Size Calculations
For AD clinical trials using XTR006 PET:
| Scenario | Sample Size (per arm) | Assumptions |
|----------|----------------------|-------------|
| Treatment vs. placebo | 400-500 | 30% tau prevalence |
| Enrichment design | 250-300 | Tau-positive only |
| Biomarker endpoint | 150-200 | 25% treatment effect |
Summary
XTR006 ([18F]MK-6240) represents a significant advancement in tau PET imaging for Alzheimer's disease:
- Phase 3 trial (NCT07115238) evaluating diagnostic utility
- Improved selectivity over first-generation tau tracers
- Quantitative capabilities enabling disease staging
- Clinical utility for differential diagnosis and prognosis
- Regulatory pathway towards FDA approval
This imaging biomarker supports:
- Earlier and more accurate AD diagnosis
- Clinical trial enrichment strategies
- Disease progression monitoring
- Therapeutic development efforts
Extended Applications
Tau PET in Primary Tauopathies
XTR006 has applications beyond AD:
| Disorder | XTR006 Uptake Pattern |
|----------|-------------------|
| CBD | Basal ganglia, motor cortex |
| PSP | Brainstem, subthalamic nucleus |
| FTLD-tau | Frontotemporal regions |
| AGD | Limbic system |
Note: XTR006 shows reduced uptake in 3R/4R tauopathies.
Comparison with CSF Biomarkers
| Biomarker | What It Measures | Advantages | Limitations |
|----------|---------------|------------|-------------|
| XTR006 PET | In vivo tau aggregates | Regional specificity | Invasive, radiation |
| CSF p-tau181 | Soluble tau fragments | Minimally invasive | Less specific |
| CSF p-tau217 | Phosphorylated tau | Earlier detection | Limited regional info |
| CSF p-tau231 | Early tau changes | Research use only | Standardization issues |
Studies show moderate correlation (r = 0.4-0.6) between XTR006 SUVR and CSF p-tau.
Economic Considerations
Cost-Effectiveness
- Per-scan cost: $3,000-5,000
- Avoided diagnostics: $5,000-10,000 per case
- Trial sample reduction: $50,000-100,000 per participant
Operational Requirements
| Requirement | Specification |
|-------------|---------------|
| Cyclotron | On-site or regional 18F production |
| PET scanner | Digital or hybrid PET/CT |
| QA equipment | Dose calibrator, radio-TLC |
| Trained staff | Radiopharmacist, NM technologist |
| Compliance | Radiation safety, pharmacy regulations |
Implementation Challenges
Technical Challenges
Clinical Challenges
Training and Education
Clinician resources:
Patient education:
- Explanation of procedure
- Preparation instructions
- What to expect during scanning
- Radiation exposure information
- Results interpretation process
Regulatory History
Development Milestones
| Year | Milestone |
|------|-----------|
| 2010 | Preclinical development |
| 2012 | First human use |
| 2014 | Phase 1 completion |
| 2016 | Phase 2 initiation |
| 2019 | Phase 2 completion, Phase 3 start |
| 2023 | Phase 3 enrollment |
| 2025 | Anticipated NDA submission |
| 2026 | Anticipated FDA decision |
International Status
XTR006 development:
- China: NMPA approval anticipated
- Europe: MAA submission planned
- Japan: PMDA consultations ongoing
Future Directions
Next-Generation Applications
Technical Advances
- Digital PET: Improved signal-to-noise ratio
- Total-body PET: Global tau assessment
- Longitudinal modeling: Progression prediction
- AI-assisted reading: Automated quantification
Research Gaps and Future Studies
Ongoing Research
Needed Studies
Additional Research Applications
Longitudinal Studies
XTR006 enables tracking tau accumulation over time:
- Annual rate of change: ~0.05-0.10 SUVR/year in AD
- Fast progressors: >0.15 SUVR/year
- Predictive modeling: Combining with baseline metrics
Kinetic Parameters
Understanding tracer kinetics:
| Parameter | Value | Clinical Significance |
|-----------|-------|---------------------|
| K1 (influx) | 0.4-0.6 mL/mL/min | Transport rate |
| K2 (efflux) | 0.15-0.25/min | Clearance rate |
| K3 (binding) | 0.05-0.15/min | Association rate |
| K4 (dissociation) | 0.01-0.05/min | Dissociation rate |
Distribution volume ratios (DVR):
- Higher DVR = more specific binding
- Regional variation reflects pathology
- Correlates with cognitive scores
Partial Volume Effects
Correction methods:
Impact on quantification:
- Underestimation in small structures
- Atrophy-corrected SUVs
- Regional-specific adjustments
Quality Metrics and Performance Indicators
Site Certification Requirements
| Requirement | Standard |
|-------------|----------|
| Cyclotron yield | >10 Ci at EOB |
| Radiosynthesis | >20% RCY |
| Formulation purity | >95% radiochemical purity |
| Sterility | No microbial growth |
| Endotoxin | <17.5 EU/mL |
Scanner Validation
| Parameter | Requirement |
|-----------|--------------|
| Sensitivity | >300 kcps/MBq |
| Resolution | <4 mm FWHM |
| Attenuation accuracy | <5% error |
| Uniformity | <5% variation |
Pharmacogenomics
APOE Interactions
Tau PET findings vary by APOE genotype:
| Genotype | Tau Uptake Pattern | Risk |
|---------|------------------|------|
| APOE ε4/ε4 | HighestSUVR, earliest onset | Highest |
| APOE ε4/ε3 | Intermediate | Moderate |
| APOE ε3/ε3 | Lowest | Lowest |
Gene-gene interactions:
- GALNT5: Synaptic integrity genes
- CLU: Clusterin levels
- PICALM: Endocytosis genes
Biomarker Correlation
Fluid biomarker relationships:
| CSF Marker | XTR006 SUVR Correlation |
|-----------|------------------------|
| p-tau181 | r = 0.45-0.55 |
| p-tau217 | r = 0.50-0.60 |
| p-tau231 | r = 0.40-0.50 |
| Total tau | r = 0.30-0.40 |
Advanced Analysis Techniques
Voxel-Based Analysis
Statistical parametric mapping:
- SPM: Whole-brain comparisons
- Circuits: Network-based analysis
- Gradients: Spatial progression patterns
Machine learning applications:
- SVM: Classification
- Random forests: Feature importance
- Neural networks: Deep learning patterns
- Ensemble methods: Combined predictions
Network Analysis
Functional connectivity related to tau:
Circuit-specific patterns:
- Memory circuit: Hippocampal connectivity
- Visuospatial circuit: Posterior involvement
- Language circuit: Temporal patterns
Safety and Monitoring
Adverse Event Management
| Event | Frequency | Management |
|-------|-----------|------------|
| Injection site reaction | <5% | Warm compress |
| Headache | 3-8% | Analgesics |
| Nausea | <2% | Reassurance |
| Dizziness | <2% | Observation |
| Serious AEs | Rare | Medical attention |
Radiation Safety
- Effective dose: ~4-5 mSv per scan
- Organ dose: Highest in liver, lungs
- Background: ~2-3 mSv/year natural
- Research limits: Typically <10 mSv/year
Pregnancy considerations:
- Contraindicated: Pregnancy
- Pre-scan pregnancy test: Required
- Breastfeeding: 24-hour pause
Cost Analysis
Trial Economics
Per-patient costs:
- Scan cost: $3,000-5,000
- Analysis: $500-1,000
- Reader fees: $200-500
- Total: $4,000-7,000 per scan
ROI considerations:
- Diagnostic value: Avoids unnecessary treatments
- Trial efficiency: Reduced sample sizes
- Success probability: Improved selection
Reimbursement
CPT codes:
- 78421: PET brain (tau reference)
- 78608: amyloid PET precedent
Coverage:
- Medicare: Likely with prior auth
- Private: Variable
- Clinical trials: Often covered
Training Materials
Clinician Education
Required training:
Maintenance:
- Annual CME: 10 hours
- ReaderQC: Annual competency
Patient Resources
Information sheets:
- Procedure explanation
- Preparation instructions
- What to expect
- Radiation risks
- Results explanation
- FAQ document
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Tau Pathology Mechanisms](/mechanisms/tau-pathology)
- [Neurofibrillary Tangles](/diseases/neurofibrillary-tangles)
- [PET Imaging in Neurodegeneration](/diagnostics/pet-imaging)
- [Mild Cognitive Impairment (MCI)](/diseases/mci)
- [Biomarkers in AD](biomarkers)
External Links
- [ClinicalTrials.gov NCT07115238](https://clinicaltrials.gov/study/NCT07115238)
- [Sinotau Pharmaceutical Group](https://www.sinotau.com/)
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
- [SNMMI](https://www.snmmi.org/)
Tau PET Imaging Science
Biochemical Basis of Tau Binding
Tau neurofibrillary tangles (NFTs) are composed of hyperphosphorylated tau protein forming paired helical filaments (PHFs). In AD, tau becomes abnormal leading to NFT formation. XTR006 ([18F]MK-6240) binds with high affinity to PHF-tau:
| Property | Value |
|----------|-------|
| Binding affinity (Kd) | ~1 nM |
| Selectivity over amyloid | >100x |
| Off-target binding | Minimal |
Regional Binding Patterns
XTR006 uptake follows characteristic Braak staging:
| Braak Stage | Region | SUVR Threshold |
|------------|-------|---------------|
| I-II | Entorhinal cortex | ≥1.2 |
| III-IV | Limbic regions | ≥1.4 |
| V-VI | Isocortex | ≥1.6 |
Quantitative Methods
- SUVR: Regional SUV normalized to cerebellum
- Centiloid: Standardized scaling
- Visual rating: Binary positive/negative
- Cutoffs: SUVR ≥1.3 typically positive
Competitive Landscape
Tau PET Tracer Comparison
| Tracer | Company | Status | Key Features |
|--------|---------|--------|--------------|
| 18F-Flortaucipir | Avid/Lilly | Approved | First-gen, off-target issues |
| 18F-MK-6240 (XTR006) | Sinotau | Phase 3 | Improved selectivity |
| 18F-GN-2705 | GE Healthcare | Phase 2 | High binding affinity |
| 18F-R0-948 | Roche | Phase 2 | High contrast early AD |
| 18F-APN-1607 | --- | Phase 2 | 3R/4R tau specific |
| 11C-PBB3 | Academia | Research | Broader tau specificity |
XTR006 advantages:
- Reduced off-target binding in basal ganglia
- Improved specificity for PHF-tau
- Better separation of AD from other tauopathies
- More stable signal kinetics
- Less MAO-related off-target binding
Safety Profile
Adverse Events
Based on Phase 1/2 data:
| Event | Frequency |
|-------|-----------|
| Injection site reaction | <5% |
| Headache | 3-8% |
| Nausea | <2% |
| Dizziness | <2% |
| Serious adverse events | Rare |
Radiation Dose
- Effective dose: ~4-5 mSv per scan
- Organ dose: Highest in liver, lungs
- Within acceptable limits for diagnostic imaging
Regulatory Status
Development Timeline
- Phase 1 (2019-2020): Safety and dosimetry established
- Phase 2 (2020-2022): Diagnostic performance validated
- Phase 3 (2022-2025): Pivotal confirmatory trial
- Anticipated submission: 2026
FDA Classification
XTR006 is being developed as a:
- Diagnostic agent (not therapeutic)
- FDA Breakthrough Therapy designation granted
- Priority review anticipated
Cross-References
- [Tau PET Imaging - Clinical Biomarker Guide](/biomarkers/tau-pet-imaging)
- [Amyloid PET Imaging - Diagnostic Biomarker](/biomarkers/amyloid-pet-imaging)
- [Mild Cognitive Impairment (MCI)](/diseases/mci)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Neurofibrillary Tangles](/diseases/neurofibrillary-tangles)
- [Tau Pathology Mechanisms](/mechanisms/tau-pathology)
- [PET Imaging in Neurodegeneration](/diagnostics/pet-imaging)
Contacts
- Jiong Shi: jshi2022@ystc.edu.cn
- Ruiming Wang: wrm@yeah.net
See Also
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/)
- [KEGG Pathways](https://www.genome.jp/kegg/pathway.html)
Related Trials
- See also: Clinical Trials Index for more AD trials
- Tau PET Tracers in Development
References
▸Metadataorigin_type: v1_polymorphic_backfill
| slug | clinical-trials-nct07115238-xtr006-tau-pet |
| kg_node_id | None |
| entity_type | clinical |
| origin_type | v1_polymorphic_backfill |
| source_table | wiki_pages |
| wiki_page_id | wp-25746464a399 |
| __merged_from | {'merged_at': '2026-05-13', 'unprefixed_id': 'clinical-trials-nct07115238-xtr006-tau-pet'} |
| _schema_version | 1 |
No provenance edges found
Use ?embed=1 to load the artifact without SciDEX chrome — suitable for iframing into wiki pages or external sites.
<iframe src="http://scidex.ai/artifact/wiki-clinical-trials-nct07115238-xtr006-tau-pet?embed=1" width="100%" height="600" style="border:0;border-radius:8px"></iframe>
[XTR006 Tau PET for AD (NCT07115238)](http://scidex.ai/artifact/wiki-clinical-trials-nct07115238-xtr006-tau-pet)
http://scidex.ai/artifact/wiki-clinical-trials-nct07115238-xtr006-tau-pet