PET/MRI Brain Imaging for Alzheimer's Disease

(PiB ADC Trial)

Overseen By Jonathan McConathy, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Alabama at Birmingham

Disqualifiers: MRI contraindication, Severe dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to image the brain for plaque build-up, which links to Alzheimer's disease. The study employs a special scan called [C-11]PiB-PET/MRI, a brain imaging technique that helps doctors determine the amount and location of these plaques in the brain. The goal is to understand how race and certain health risks might affect brain health and cognitive skills in people with Alzheimer's. Individuals already participating in the UAB Alzheimer's study who can undergo MRI and PET scans might be suitable for this trial. As a Phase 2 trial, this research focuses on assessing the effectiveness of the imaging technique in an initial, smaller group, offering participants a chance to contribute to significant advancements in Alzheimer's diagnostics.

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 prior data suggests that this PET/MRI technique is safe for brain imaging?

Research has shown that the [C-11]PiB-PET/MRI method primarily detects amyloid plaques in the brain, which are linked to Alzheimer's disease. This imaging technique uses a special substance called [C-11]PiB to make these plaques visible on PET scans.

In past studies, patients generally tolerated [C-11]PiB well, with no major safety issues reported. This tracer allows doctors to see brain changes related to Alzheimer's more clearly than other imaging methods. While the main focus has been on its effectiveness, available safety data suggests it is safe for humans, as it has been used in clinical settings for a long time.

The current trial is a Phase 2 study, indicating that earlier studies have shown the treatment to be safe enough to test its effectiveness. This should reassure potential participants about the safety of [C-11]PiB-PET/MRI. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike traditional treatments for Alzheimer's disease that mainly focus on managing symptoms with medications like donepezil or memantine, the [C-11]PiB-PET/MRI approach offers a unique diagnostic advantage. This method utilizes a radioactive tracer, [C-11]PiB, in combination with PET/MRI imaging to detect amyloid plaques in the brain, which are a hallmark of Alzheimer's. Researchers are excited about this technique because it allows for early and accurate detection of amyloid deposits, potentially leading to earlier intervention and improved outcomes. This imaging method could transform how Alzheimer's is diagnosed and monitored, providing a clearer picture of the disease's progression.

What evidence suggests that this PET/MRI technique is effective for Alzheimer's Disease?

Research has shown that the [C-11]PiB-PET/MRI imaging technique, which all participants in this trial will undergo, is useful for diagnosing Alzheimer's disease. Studies have found that it can accurately differentiate between Alzheimer's, other types of dementia, and mild cognitive impairment (MCI). This method uses a special tracer, [C-11]PiB, which attaches to amyloid plaques in the brain—key indicators of Alzheimer's. Seeing these plaques makes identifying the disease easier, especially when the diagnosis is uncertain. Overall, [C-11]PiB-PET/MRI provides clearer and more reliable images than other imaging methods. ^{2 6 7 8 9}

Who Is on the Research Team?

Jonathan McConathy, MD, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• [C-11]PiB-PET/MRI

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.

How Is the Trial Designed?

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+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

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 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]

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]

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]

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]

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 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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26085054/

Clinical impact of (11)C-Pittsburgh compound-B positron ... (11)C-PiB PET may be of value in making the diagnosis of dementia and MCI in cases with high diagnostic uncertainty.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0925492715300032

Combination of dynamic 11 C-PIB PET and structural MRI ... We adopted a linear sparse support vector machine to build classifiers for distinguishing AD and MCI subjects from cognitively normal (CN) ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/17420404/

11C-PIB PET imaging in Alzheimer disease and ... - PubMed PET imaging with (11)C-labeled Pittsburgh Compound-B ((11)C-PIB) helps discriminate Alzheimer disease (AD) from frontotemporal lobar degeneration (FTLD).

4. jnm.snmjournals.org jnm.snmjournals.org/content/48/4/547

Visual Assessment Versus Quantitative Assessment of 11 C ... 11 C-PIB PET images appear easier to read and more accurate than 18 F-FDG PET images in AD diagnosis, particularly in older subjects.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1936878X20302473

Diagnostic Accuracy of [11C]PIB Positron Emission ... [ 11 C]PIB PET was highly accurate in detecting cardiac involvement in the main amyloid subtypes, with 100% accuracy in AL amyloidosis.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7837835/

Clinical impact of 11C-Pittsburgh compound-B positron ... This study aimed to evaluated the clinical impact of adding 11 C Pittsburgh compound-B ( 11 C-PiB) PET for clinical diagnosis of mild cognitive impairment (MCI ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0197458008000353

Clinical severity of Alzheimer's disease is associated with ... The positron emission tomography (PET) tracer [11C]-Pittsburgh Compound-B ([11C]PIB) allows the in vivo assessment of amyloid plaque burden in the brain.

8. jamanetwork.com jamanetwork.com/journals/jamaneurology/fullarticle/1107806

Using Positron Emission Tomography and Carbon 11 ... Dynamic [ 11 C]PiB PET can be used successfully to measure cerebral β-amyloid deposition in DS. A clinical diagnosis of AD and age appear to be predictors.

9. e-century.us e-century.us/files/ajnmmi/14/1/ajnmmi0154938.pdf

Two decades of [11C]PiB synthesis, 2003-2023: a review Alzheimer's disease (AD) is the most common neurode- generative disorder associated with progressive memory loss and cognitive impairment AD is ...