April 18th, 2025
This protocol describes the use of 18F-AV-1451 PET/MRI to reveal tau pathology and neurodegeneration, aiding neurologists in diagnosing Alzheimer's disease, assessing its severity, and gaining insights into its progression and underlying pathological mechanisms.
This research focuses on developing a brain scanning method for early detection of Alzheimer's disease, assessing its severity and tracking the accumulation of harmful tau proteins. PET/MRI combines both PET and MRI. MIRI reveals atrophy and the PET detects tau. One scan, two answers is faster, safer, and tells the full story without the need for additional tests. In the future, our laboratory will aim to improve transfer quality with a focus on conducting test scans across different groups and studying how tau interacts with other brain damaging proteins.
[Narrator] To begin, verify the application form to confirm general information, examination purpose and program. Ensure that all necessary preparations have been completed. Register and file the details. After obtaining informed consent for PET/MR imaging from the subject or a family member, conduct a detailed medical history review and record the subject's height and weight. Now, establish an intravenous line in a peripheral superficial vein or access a port catheter. Inject fluorine 18-AV-1451 at a dose of 3.7 to 5.5 megabecquerel per kilogram slowly through intravenous access. Flush the tube with an appropriate amount of saline to minimize radioactive tracer residue. Apply compression to the injection site to prevent fluid leakage. Record the injection time, site, and activity. After completing the injection, initiate audio-visual closure by dimming the lights in the restroom and setting the temperature to approximately 22 degrees Celsius. Instruct the subject to rest in bed for 80 minutes, avoiding talking, eating, or chewing during this period. Instruct the subject and companion to remove all metallic objects, including mobile phones, headgear, dentures, glasses, watches, wallets, and coins before the examination. Provide earplugs to the subject and position them supine on the PET/MRI table. With an eight-channel head and neck union coil enclosing the cervical region, position the subject with arms down and instruct them to use the alarm device in case of discomfort. Review the images to confirm that the head is centered in the scanner, aligned with the center of the coil and positioned consistently relative to the neck. Acquire three-dimensional brain volumetric T1 weighted sequences with high resolution and a high signal to noise ratio using a spoiled gradient recalled sequence. Then, acquire axial propeller T2 weighted sequences. Acquire 20-minute PET images simultaneously in 3D acquisition mode and using volumetric scanning. Perform MR imaging attenuation correction using a zero echo time pulse sequence to segment bone, air, and soft tissue. Finally, use the given parameters to acquire PET data using the time of flight ordered subset expectation maximization for image reconstruction. A typical semi-preparative HPLC and UV spectrum of fluorine 18-AV-1451 is shown in this figure where peak 2 represents the product peak. The one-step synthesis of fluorine 18-AV-1451 under optimized reaction conditions increased the synthesis yield to above 25.7%. The total reaction time was 70 minutes. The fluorine 18-AV-1451 PET/MR imaging of a 69-year-old patient with cognitive decline and positive tau deposition showed significant brain atrophy and tau accumulation beginning in the entorhinal cortex and hippocampus, spreading to the temporal, parietal, and cortical regions. The fluorine 18-AV-1451 PET/MR imaging of a 68-year-old patient with cognitive decline and negative tau deposition showed a normal brain structure and uniform radioactivity uptake without specific cortical tau binding.
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This protocol describes the use of 18 F-AV-1451 PET/MRI to reveal tau pathology and neurodegeneration, aiding neurologists in diagnosing Alzheimer's disease, assessing its severity, and gaining insights into its progression and underlying pathological mechanisms.
Hybrid PET/MRI imaging with 18F-AV-1451 enables direct visualization of tau pathology and neurodegeneration in Alzheimer's disease, supporting early discovery and mechanistic de-risking in neurodegenerative pipeline programs. This integrated approach enhances predictive confidence for target engagement and disease progression, informing portfolio triage and translational continuity. The method's quantitative outputs and dual-modality readouts position it as a reusable capability for biomarker-driven R&D in CNS disorders.
This hybrid PET/MRI protocol integrates from early discovery through translational research, providing a bridge between mechanistic studies and clinical biomarker validation in Alzheimer's disease.