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. This Phase 3 clinical trial (NCT07115238) aims to establish the diagnostic utility of XTR006 for detecting and quantifying tau pathology in vivo.
Tau neurofibrillary tangles are one of the hallmark pathological features of Alzheimer's disease and closely correlate with cognitive decline. 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.
The ability to visualize tau pathology non-invasively addresses several unmet needs:
- 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
| 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; Neurofibrillary Tangle |
| Last Updated |
August 2025 |
[18F]XTR006 (also known as [18F]MK-6240 or Florquinitau) is a PET radiopharmaceutical that selectively binds to tau 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 and other tauopathies.
The trial enrolls participants aged 50 years and older in three diagnostic groups:
- **Alzheimer's Disease (AD)** - Meet 2014 IWG-2 criteria, positive Aβ-PET
- **Mild Cognitive Impairment (MCI)** due to AD - Meet 2011 NIA-AA criteria, positive Aβ-PET
- Cognitively normal controls - CDR=0, MMSE≥28, negative Aβ-PET
- Age ≥50 years
- Male or female participants
- Able to tolerate PET and MRI procedures
- 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
- 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
- Sensitivity and specificity of XTR006 PET visual reading for detecting tau NFTs compared to truth standard
- Timeframe: 12 months
- Brain uptake patterns/SUVR comparisons across MCI, AD, and cognitively normal groups
- Safety and tolerability profile via adverse events monitoring
- Timeframe: 12 months
This trial represents a significant advancement in tau PET imaging for Alzheimer's Disease diagnostics. Tau neurofibrillary tangles are closely correlated with cognitive decline in AD, and their visualization enables:
- 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:
- [18F]XTR006 targets the T (tau) component
- Used in conjunction with amyloid PET (A component)
- Provides complementary information to neuroimaging markers of neurodegeneration
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
| 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 |
- 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
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 |
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
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 |
| Modality |
Information Gained |
| Amyloid PET |
Amyloid-tau relationship |
| FDG PET |
Metabolic dysfunction |
| MRI |
Structural changes |
| CSF biomarkers |
Fluid biomarker correlation |
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
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 |
- Fasting ≥6 hours (not strictly required)
- Hydration with water
- Void bladder before scan
- Relax in quiet room 30 minutes before injection
- 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
- Uptake period: 75-115 minutes post-injection
- Scan duration: 20-30 minutes
- Optional delayed scan: 90-130 minutes
- Reconstruction: OSEM or TOF OSEM
- Attenuation correction: CT or MR-based
- Motion correction: Frame-by-frame registration
- Spatial normalization: MNI template
- Quantification: ROI-based and voxel-wise
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 |
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
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.
| 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.
- Per-scan cost: $3,000-5,000
- Avoided diagnostics: $5,000-10,000 per case
- Trial sample reduction: $50,000-100,000 per participant
| 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 |
- Radiochemistry: Specialized synthesis equipment
- Quality control: Rigorous release criteria
- Standardization: Scanner and protocol harmonization
- Quantification accuracy: Partial volume effects
- Referral patterns: Neuroradiologist training
- Interpretation variability: Reader training and QA
- Clinical integration: Workflow adaptation
- Reimbursement: Payer negotiations
¶ Training and Education
Clinician resources:
- Online modules: Self-paced learning
- Case libraries: Standardized cases
- Certification: Reader competency testing
- Maintenance: Annual continuing education
Patient education:
- Explanation of procedure
- Preparation instructions
- What to expect during scanning
- Radiation exposure information
- Results interpretation process
| 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 |
XTR006 development:
- China: NMPA approval anticipated
- Europe: MAA submission planned
- Japan: PMDA consultations ongoing
- Early detection: Identifying tau in preclinical AD
- Combination PET: Simultaneous amyloid-tau imaging
- Therapeutic monitoring: Anti-tau antibody efficacy
- Prognostic modeling: Predictive algorithms
- 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
- Longitudinal validation: 5-year follow-up studies
- Population norms: Reference values across demographics
- Combination therapies: Anti-amyloid + anti-tau
- Prevention trials: Preclinical enrollment
- Head-to-head comparison: XTR006 vs. flortaucipir
- Autopsy correlation: Larger post-mortem series
- Pediatric applications: Not applicable
- Diversity studies: Multiethnic validation
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
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
Correction methods:
- Recovery coefficients: Regional lookup
- FWHM-based correction: Resolution matching
- PCA-based correction: Template-based
- ML-based correction: Learning approaches
Impact on quantification:
- Underestimation in small structures
- Atrophy-corrected SUVs
- Regional-specific adjustments
| 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 |
| Parameter |
Requirement |
| Sensitivity |
>300 kcps/MBq |
| Resolution |
<4 mm FWHM |
| Attenuation accuracy |
<5% error |
| Uniformity |
<5% variation |
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
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 |
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
Functional connectivity related to tau:
- Default mode network: Tau-related disruption
- Salience network: Relationship with cognitive decline
- Executive network: Frontal involvement
Circuit-specific patterns:
- Memory circuit: Hippocampal connectivity
- Visuospatial circuit: Posterior involvement
- Language circuit: Temporal patterns
¶ Safety and Monitoring
| Event |
Frequency |
Management |
| Injection site reaction |
<5% |
Warm compress |
| Headache |
3-8% |
Analgesics |
| Nausea |
<2% |
Reassurance |
| Dizziness |
<2% |
Observation |
| Serious AEs |
Rare |
Medical attention |
- 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
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
CPT codes:
- 78421: PET brain (tau reference)
- 78608: amyloid PET precedent
Coverage:
- Medicare: Likely with prior auth
- Private: Variable
- Clinical trials: Often covered
Required training:
- Physics: 4 hours
- Radiation safety: 2 hours
- Image interpretation: 8 hours
- Case review: 20 cases
- Certification: Written exam
Maintenance:
- Annual CME: 10 hours
- ReaderQC: Annual competency
Information sheets:
- Procedure explanation
- Preparation instructions
- What to expect
- Radiation risks
- Results explanation
- FAQ document
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 |
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 |
- SUVR: Regional SUV normalized to cerebellum
- Centiloid: Standardized scaling
- Visual rating: Binary positive/negative
- Cutoffs: SUVR ≥1.3 typically positive
¶ Competitive Landscape
| 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
Based on Phase 1/2 data:
| Event |
Frequency |
| Injection site reaction |
<5% |
| Headache |
3-8% |
| Nausea |
<2% |
| Dizziness |
<2% |
| Serious adverse events |
Rare |
- Effective dose: ~4-5 mSv per scan
- Organ dose: Highest in liver, lungs
- Within acceptable limits for diagnostic imaging
- 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
XTR006 is being developed as a:
- Diagnostic agent (not therapeutic)
- FDA Breakthrough Therapy designation granted
- Priority review anticipated
- See also: Clinical Trials Index for more AD trials
- Tau PET Tracers in Development