PET/MRI Brain Imaging for Alzheimer's Disease

(PiB ADC Trial)

Overseen by Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Alabama at Birmingham

Disqualifiers: MRI contraindication, Severe dementia, others

No Placebo Group

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial uses a special imaging dye to detect harmful protein build-up in the brains of participants from the UAB Alzheimer's Disease Center. The study aims to understand how these brain changes relate to race, vascular risk factors, and cognitive health. The dye helps make these harmful proteins visible in brain scans.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment [C-11]PiB-PET/MRI for Alzheimer's disease?

Research shows that the [C-11]PiB-PET imaging can help identify amyloid-beta plaques in the brain, which are associated with Alzheimer's disease. This imaging technique has been used to distinguish Alzheimer's from other types of dementia and to assess changes in amyloid-beta levels in patients undergoing treatment. ^{1 2 3 4 5}

Is [C-11]PiB-PET/MRI safe for humans?

The research does not provide specific safety data for [C-11]PiB-PET/MRI, but it is widely used in clinical studies for imaging amyloid plaques in Alzheimer's disease, suggesting it is generally considered safe for human use in this context. ^{6 7 8 9 10}

How does the PET/MRI brain imaging treatment for Alzheimer's differ from other treatments?

This treatment uses a special imaging technique with a radiotracer called Pittsburgh compound-B (11C-PIB) to detect amyloid plaques in the brain, which are associated with Alzheimer's disease. Unlike other treatments that may focus on symptoms or slowing disease progression, this approach is unique because it helps visualize the presence of amyloid plaques, aiding in diagnosis and understanding of the disease. ^{1 6 7 8 11}

Research Team

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for participants already enrolled in the UAB Alzheimer's Disease Center study. It's focused on those who can undergo PET/MRI scans and do not have severe dementia that would prevent participation. Women of childbearing potential must test negative for pregnancy.

Inclusion Criteria

Enrollment in the UAB-ADC study under a separate IRB-approved research protocol (IRB-300000169)

I am not pregnant or have been menopausal for over a year or am surgically sterilized.

Exclusion Criteria

Meets any exclusion criteria for the UAB-ADC study (IRB-300000169)

Inability or contraindication for undergoing MRI and/or PET imaging

Inability to participate in the imaging studies due to severity of dementia

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo amyloid-PET imaging using the tracer [C-11]PiB with a simultaneous PET/MRI system

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

5 years

Treatment Details

Interventions

• [C-11]PiB-PET/MRI (PET tracer)

Trial Overview The study aims to measure amyloid deposits in the brain using a PET tracer called [C-11]PiB. It will explore how race and vascular risk factors interact with these amyloid levels and cognitive status.

Participant Groups

Group I: [C-11]PiB-PET/MRI Experimental Treatment 1 Intervention

All participants in this study will undergo an amyloid-PET imaging using the tracer \[C-11\]PiB with a simultaneous PET/MRI system. The \[C-11\]PiB dosage is 300-670 MBq (8 - 18 mCi) given intravenously, and the PET/MRI imaging time is approximately 60 min.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Kierstin Kennedy

University of Alabama at Birmingham

Chief Medical Officer since 2022

MD

S. Dawn Bulgarella

University of Alabama at Birmingham

Chief Executive Officer since 2023

BSc in Commerce and Business Administration from the University of Alabama, MS in Health Administration from the University of Alabama at Birmingham

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Dr. Richard J. Hodes

National Institute on Aging (NIA)

Chief Executive Officer since 1993

MD from Harvard Medical School

Dr. Marie Bernard

National Institute on Aging (NIA)

Chief Medical Officer

MD from Harvard Medical School

Findings from Research

In a study of 69 patients with mild cognitive impairment (MCI), 56% showed retention of the (11)C-PIB radiotracer, indicating amyloid plaque presence, with a higher prevalence in amnestic-MCI (68%) compared to non-amnestic-MCI (19%).

Among the (11)C-PIB positive patients, a majority exhibited a B-pattern of retention, suggesting that this pattern may be more common and could provide insights into potential therapeutic strategies for MCI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns of 11C-PIB cerebral retention in mild cognitive impairment patients. Banzo, I., Jiménez-Bonilla, JF., Martínez-Rodríguez, I., et al.[2018]

In a study of 57 memory clinic patients, the use of (11)C-PiB-PET scans helped reclassify the diagnoses of 23% of patients, indicating its potential to improve diagnostic accuracy for Alzheimer's disease.

The confidence of clinicians in their diagnoses increased for nearly half (49%) of the patients after reviewing the PiB-PET results, suggesting that this imaging technique enhances the overall diagnostic process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Added Diagnostic Value of (11)C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis. Frederiksen, KS., Hasselbalch, SG., Hejl, AM., et al.[2021]

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]

Visual assessment of [(11)C]PIB PET images demonstrated high accuracy and reliability as a supportive diagnostic marker for Alzheimer's disease, with excellent inter-rater agreement and a sensitivity and specificity of 95%.

In contrast, visual assessment of [(18)F]FDDNP PET images was found to be insufficient, with lower sensitivity and specificity, indicating that quantitative analysis of [(18)F]FDDNP data is more valuable for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images. Tolboom, N., van der Flier, WM., Boverhoff, J., et al.[2020]

PET imaging with (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) effectively distinguishes Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD), with all AD patients showing positive scans compared to most FTLD patients and controls who had negative scans.

The study involved 27 participants (7 with AD, 12 with FTLD, and 8 cognitively normal controls), and results indicated that mean distribution volume ratios (DVRs) were significantly higher in AD patients than in FTLD patients, suggesting that (11)C-PIB can be a useful tool for diagnosing these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. Rabinovici, GD., Furst, AJ., O'Neil, JP., et al.[2020]

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]

The new (18)F-labeled Aβ tracer, (18)F-AZD4694, shows similar binding kinetics and imaging characteristics to the established (11)C-PiB tracer, making it a promising alternative for detecting β-amyloid plaques in Alzheimer's disease.

Both tracers demonstrated low nonspecific white matter binding and high cortical binding, indicating that (18)F-AZD4694 is effective for accurate imaging in both clinical and research settings, with excellent correlation in results between the two tracers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. Rowe, CC., Pejoska, S., Mulligan, RS., 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]

A new fully-automated procedure for synthesizing [(11)C]PIB, a key PET compound for Alzheimer imaging, has been developed, achieving a high specific activity of 183±14 GBq/μmol and over 99% radiochemical purity.

The optimized synthesis process takes only 40 minutes from the end of bombardment (EOB) and produces enough [(11)C]PIB to serve two patients, enhancing the efficiency and reliability of Alzheimer imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB). Philippe, C., Haeusler, D., Mitterhauser, M., et al.[2020]

The study found that 11C-Pittsburgh Compound B (11C-PiB) binds nonspecifically to white matter in the brain, indicating that its retention in white matter does not correlate with the presence of amyloid-beta plaques, which are associated with Alzheimer's disease.

In contrast, 11C-PiB showed significantly higher retention in the gray matter of Alzheimer's patients compared to healthy controls, suggesting that the observed differences in PiB retention are primarily due to its specific binding to amyloid plaques in gray matter rather than in white matter.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of PiB binding to white matter in Alzheimer disease and other dementias. Fodero-Tavoletti, MT., Rowe, CC., McLean, CA., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Patterns of 11C-PIB cerebral retention in mild cognitive impairment patients. [2018]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Added Diagnostic Value of (11)C-PiB-PET in Memory Clinic Patients with Uncertain Diagnosis. [2021]

3. 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]

4. England pubmed.ncbi.nlm.nih.gov

Molecular imaging in the diagnosis of Alzheimer's disease: visual assessment of [11C]PIB and [18F]FDDNP PET images. [2020]

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

11C-PIB PET imaging in Alzheimer disease and frontotemporal lobar degeneration. [2020]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Head-to-head comparison of 11C-PiB and 18F-AZD4694 (NAV4694) for β-amyloid imaging in aging and dementia. [2021]

8. England pubmed.ncbi.nlm.nih.gov

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

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

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

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

Optimization of the radiosynthesis of the Alzheimer tracer 2-(4-N-[11C]methylaminophenyl)-6-hydroxybenzothiazole ([11C]PIB). [2020]

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

Characterization of PiB binding to white matter in Alzheimer disease and other dementias. [2022]