Molecular and Structural Imaging for Alzheimer's Disease

Overseen By Sarah M Boland, CCRP

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Chemotherapy

Disqualifiers: Stroke, Tumor, Poor vision, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you may be excluded if you are on medications that affect brain structure or metabolism, like chemotherapy.

What data supports the effectiveness of the drug C-11 PiB, Pittsburgh Compound B, [11C]6-OH-BTA-1, (N-Methyl-[11C])2-(4'-methylamino-phenyl)-6-hydroxy-benzo-thiazole, [11C]PiB, F-18 AV 1451, Tauvid, Flortaucipir F-18, 18F-AV-1451, 18F-T807, LY-3191748, T-807 F-18 for Alzheimer's disease?

Research shows that Flortaucipir F-18, a component of the drug, is effective in imaging tau protein tangles, which are a key feature of Alzheimer's disease. This helps in diagnosing and understanding the progression of the disease by showing the distribution and density of these tangles in the brain. ^{1 2 3 4 5}

Is the imaging treatment for Alzheimer's disease safe for humans?

The imaging agents like Pittsburgh compound B and flortaucipir have been used in many studies for Alzheimer's disease and other conditions, and they are generally considered safe for human use in clinical settings. ^{6 7 8 9 10}

How does the treatment in the Alzheimer's imaging trial differ from other treatments?

This treatment uses advanced imaging techniques like PET scans with specific tracers to visualize and measure amyloid and tau proteins in the brain, which are associated with Alzheimer's disease. Unlike traditional treatments that focus on symptom management, this approach aims to provide a detailed understanding of the disease's progression and response to potential therapies. ^{1 8 10 11 12}

What is the purpose of this trial?

This is a neuroimaging study designed to learn more about amyloid and tau burden in the brain of patients with typical and atypical Alzheimer's Disease and how burden may change over a one year period.

Research Team

Jennifer Whitwell, Ph.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

This study is for adults over 21 with Atypical Alzheimer's Disease, specifically those diagnosed with Logopenic Aphasia or Posterior Cortical Atrophy. Participants must have a person to report on their functioning and speak English as their primary language. They can't join if they've had strokes, tumors, severe memory issues early on, other neurodegenerative diseases, very poor vision, are pregnant/breastfeeding, or have MRI contraindications.

Inclusion Criteria

I have trouble finding the right words and forming sentences.

I have Alzheimer's with worsening memory loss or specific symptoms like LPA or PCA.

English is primary language

Exclusion Criteria

I do not have any other neurodegenerative disorders like frontotemporal dementia.

Subjects will also be excluded if MRI is contraindicated (metal in head, cardiac pace maker, e.t.c.), if there is severe claustrophobia, if there are conditions that may confound brain imaging studies (e.g. structural abnormalities, including subdural hematoma or intracranial neoplasm), or if they are medically unstable or are on medications that might affect brain structure or metabolism (e.g. chemotherapy)

I have had a stroke or tumor that might be causing my symptoms.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo two Tau PET scans and two PiB PET scans to assess amyloid and tau burden

12 months

Follow-up

Participants are monitored for changes in amyloid and tau burden over a one year period

4 weeks

Treatment Details

Interventions

• C-11 PiB
• F-18 AV 1451

Trial Overview The trial is using advanced brain imaging techniques (F-18 AV 1451 and C-11 PiB) to investigate the presence of amyloid and tau proteins in patients' brains. It aims to see how these protein levels change over one year in individuals with atypical forms of Alzheimer's disease.

Participant Groups

Group I: Tau PET Scan, F-18 AV 1451 Experimental Treatment 2 Interventions

All subjects will receive two Tau PET scans during this study.

Group II: PiB PET Scan, C-11 PiB Experimental Treatment 2 Interventions

All subjects will receive two PiB PET scans during this study.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Findings from Research

This study found a strong correlation (Pearson r = 0.81) between flortaucipir PET imaging results and levels of abnormally phosphorylated tau (Ptau) in brain tissue from patients with dementia, suggesting that flortaucipir can effectively reflect tau pathology in Alzheimer's disease.

The research indicates that while flortaucipir PET correlates well with Ptau levels, it does not show a significant relationship with amyloid-β (Aβ1-42), highlighting its potential specificity for tau-related changes in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. Pontecorvo, MJ., Keene, CD., Beach, TG., et al.[2021]

18F-Florbetapir PET imaging is effective for detecting β-amyloid plaques, while 18F-Flortaucipir PET is useful for visualizing tau protein tangles, both of which are critical for diagnosing Alzheimer's disease (AD).

Combining data from both amyloid and tau PET scans can enhance the accuracy of differential diagnosis and prognosis in patients with mild cognitive impairment or suspected AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series. James, OG., Linares, AR., Hellegers, C., et al.[2023]

The [18F]flortaucipir PET imaging technique has demonstrated high affinity for tau proteins associated with Alzheimer's disease and shows excellent accuracy in distinguishing AD from other conditions, indicating strong analytical and clinical validity.

While phases 1 and 2 of the maturity assessment for [18F]flortaucipir PET have been largely achieved, further research is needed to fully establish its clinical utility, particularly in early detection and healthcare outcomes for patients with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase biomarker development framework. Wolters, EE., Dodich, A., Boccardi, M., et al.[2021]

Flortaucipir PET imaging shows a strong correlation with tau burden in Alzheimer's disease (AD), indicating its effectiveness in evaluating tau levels in AD patients, although there are exceptions where the uptake does not match due to other conditions.

In contrast, flortaucipir has limited effectiveness in assessing tau burden in non-Alzheimer's tauopathies, suggesting a need for improved imaging techniques to better detect tau in these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer's & frontotemporal lobar degeneration patients. Gatto, RG., Carlos, AF., Reichard, RR., et al.[2023]

The review highlights that various tau PET tracers, including the FDA-approved 18F-flortaucipir, effectively discriminate between Alzheimer's disease (AD) patients and healthy controls, with effect sizes (Cohen's d) typically ranging from two to three in affected brain regions.

While second-generation tau tracers show improved off-target binding profiles, they do not significantly enhance sensitivity for distinguishing AD from healthy controls, suggesting a potential limit in the affinity of current tracers for tau fibrils.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET. Mohammadi, Z., Alizadeh, H., Marton, J., et al.[2023]

The FDA-approved radiotracer 18F-flortaucipir is increasingly used in PET imaging to visualize tau pathology in patients with cognitive impairment, particularly Alzheimer's disease.

An international consensus has been established to standardize the procedural use of 18F-flortaucipir PET imaging, which will enhance its application in clinical practice for diagnosing and managing Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. Tian, M., Civelek, AC., Carrio, I., et al.[2022]

The first fully automated synthesis of the radiotracer [11C]PIB for imaging amyloid plaques in Alzheimer's disease was successfully developed, allowing for efficient production in clinical settings.

This automated process yields [11C]PIB with a high radiochemical purity of over 99% and a specific activity of 20-60 GBq/micromol, enabling timely preparation for PET scans within 25 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer. Verdurand, M., Bort, G., Tadino, V., et al.[2020]

A strong correlation was found between the retention ratios of (11)C-Pittsburgh compound B (PiB) and (18)F-florbetapir in the same individuals, indicating that both radioligands effectively measure amyloid-β levels in the brain, with a Spearman correlation coefficient ranging from 0.86 to 0.95.

The study established reliable cutoff thresholds for determining amyloid-β positivity or negativity that can be interconverted between PiB and florbetapir, enhancing the consistency of diagnostic criteria across different imaging methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. Landau, SM., Breault, C., Joshi, AD., et al.[2022]

The use of [18F]PM-PBB3 tau PET imaging successfully identified tau deposition in a patient with frontotemporal dementia (FTD) caused by a MAPT mutation, indicating its potential as a diagnostic tool for this condition.

In a comparison of tau PET tracers, [18F]PM-PBB3 showed positive retention in all patients with both 3-repeat and 4-repeat tau, while AV-1451 was less consistent, highlighting [18F]PM-PBB3's broader utility in detecting tau strains associated with FTD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. Su, Y., Fu, J., Yu, J., et al.[2021]

In a study involving 30 participants (11 with semantic dementia, 9 with Alzheimer's disease, and 10 healthy controls), only a minority of early-onset semantic dementia patients showed amyloid-β deposition, while late-onset semantic dementia patients were PIB-negative, suggesting a lack of Aβ accumulation in this group.

The findings indicate that amyloid-β deposition is not associated with late-onset semantic dementia, and while some early-onset patients may exhibit Aβ deposition, they do not present the typical memory or visuospatial deficits seen in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid deposition in semantic dementia: a positron emission tomography study. Brown, EE., Graff-Guerrero, A., Houle, S., et al.[2021]

In a study involving 17 Alzheimer's disease (AD) patients and 11 healthy controls, PET imaging with the tracer [(11)C]PIB showed significantly increased uptake in several brain regions, indicating higher amyloid accumulation in AD patients.

The most notable increases in [(11)C]PIB uptake were found in the frontal cortex (163% of control mean) and posterior cingulate (146%), aligning with known patterns of amyloid pathology in Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. Kemppainen, NM., Aalto, S., Wilson, IA., et al.[2020]

In a study involving 28 patients with mild-to-moderate Alzheimer's disease, treatment with bapineuzumab significantly reduced cortical fibrillar amyloid-beta load as measured by (11)C-PiB PET scans over 78 weeks, showing a mean difference of -0.24 compared to placebo.

While most adverse events were mild to moderate, two patients experienced transient cerebral vasogenic edema, indicating that while bapineuzumab is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. Rinne, JO., Brooks, DJ., Rossor, MN., et al.[2021]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer's disease pathology: a clinicopathological study. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Evaluating Alzheimer Disease With Flortaucipir and Florbetapir PET: A Clinical Case Series. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer's disease in the context of a structured 5-phase biomarker development framework. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Comparative assessment of regional tau distribution by Tau-PET and Post-mortem neuropathology in a representative set of Alzheimer's & frontotemporal lobar degeneration patients. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Sensitivity of Tau Tracers for the Discrimination of Alzheimer's Disease Patients and Healthy Controls by PET. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

International consensus on the use of tau PET imaging agent 18F-flortaucipir in Alzheimer's disease. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Automated radiosynthesis of the Pittsburg compound-B using a commercial synthesizer. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Amyloid-β imaging with Pittsburgh compound B and florbetapir: comparing radiotracers and quantification methods. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Tau PET Imaging with [18F]PM-PBB3 in Frontotemporal Dementia with MAPT Mutation. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Amyloid deposition in semantic dementia: a positron emission tomography study. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Voxel-based analysis of PET amyloid ligand [11C]PIB uptake in Alzheimer disease. [2020]

12. England pubmed.ncbi.nlm.nih.gov

11C-PiB PET assessment of change in fibrillar amyloid-beta load in patients with Alzheimer's disease treated with bapineuzumab: a phase 2, double-blind, placebo-controlled, ascending-dose study. [2021]