PET Imaging for Alzheimer's Disease

Overseen By Tara N Turon, C.R.N.P.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: NSAIDs, Aspirin, Corticosteroids, Immunosuppressants

Disqualifiers: HIV, Pregnancy, Substance use disorder, others

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

Compensation: Varies

Number of Visits: 3

184 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if inflammation markers, COX-1 and COX-2, are elevated in the brains of individuals with neurodegenerative diseases, such as Alzheimer's, compared to healthy individuals. Participants will undergo PET scans with special tracers, including 18f-florbetaben (Neuraceq), to visualize brain inflammation. The trial is open to adults diagnosed with conditions like Alzheimer's, Huntington's, or ALS, as well as healthy volunteers. Participants must be in good general health and able to undergo MRI and PET scans.

As a Phase 1 trial, this research seeks to understand how the treatment functions in people, offering participants the chance to contribute to groundbreaking insights into brain inflammation.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before participating. Specifically, you should not have taken Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) for two weeks before the PET scan, and aspirin, corticosteroids (except skin products), or immunosuppressants must not have been taken in the prior month.

What prior data suggests that this PET imaging technique is safe for participants?

Research shows that PET imaging treatments using 11C-MC1, 11C-PS13, and 18f-florbetaben have been studied for safety. Here's a simple breakdown for each:

1. **11C-MC1**: Researchers are exploring this as a potential method to image brain inflammation related to diseases like Alzheimer's. However, limited safety information is available for humans, necessitating further research to understand its safety.

2. **11C-PS13**: Studies indicate that 11C-PS13 targets a specific protein in the brain, aiding imaging. However, these studies do not provide clear safety information, so caution is advised until more is known.

3. **18f-florbetaben**: The FDA has approved this for imaging brain plaques linked to Alzheimer's disease. It is generally considered safe when used with proper precautions to limit radiation exposure.

In summary, while 18f-florbetaben has a well-established safety record, the other two treatments are still under evaluation. Participants should be aware that research on their safety is ongoing. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these imaging agents—11C-MC1, 11C-PS13, and 18f-florbetaben—because they offer a new way to visualize and understand Alzheimer's disease in the brain. Unlike current treatments that primarily focus on managing symptoms, these imaging agents can highlight specific proteins and structures associated with Alzheimer's, potentially allowing for earlier and more accurate diagnosis. By providing detailed images of the brain, these agents could revolutionize how we detect and monitor the progression of Alzheimer's, paving the way for more targeted and effective treatments in the future.

What evidence suggests that this trial's treatments could be effective for Alzheimer's disease?

Research shows that the radiotracer 11C-MC1 can measure levels of the COX-2 enzyme in the brain, linked to inflammation in diseases like Alzheimer's. In studies with specially bred mice, 11C-MC1 successfully attached to its target, suggesting similar effectiveness in humans. For 11C-PS13, research indicates it binds well to COX-1 in the brain, aiding understanding of inflammation in conditions such as Alzheimer's. Additionally, the 18f-florbetaben PET scan has accurately detected amyloid plaques in the brain, with 81% sensitivity and 79% specificity, aiding early Alzheimer's diagnosis. These findings suggest these imaging tools may help identify inflammation and amyloid plaques in neurodegenerative diseases. In this trial, all participants will undergo the same tests, using these imaging tools to further explore their effectiveness in detecting Alzheimer's-related changes in the brain. ^{1 2 5 6 7}

Who Is on the Research Team?

Robert B Innis, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

This trial is for adults over 18 with neurodegenerative diseases like Alzheimer's, Parkinson's, or ALS and are in good health. It also includes healthy volunteers from specific NIMH studies. Participants must understand the study, sign consent, have no major neurological issues besides their diagnosis, not be on certain anti-inflammatory drugs or immunosuppressants recently, and can't be pregnant or HIV positive.

Inclusion Criteria

Healthy volunteer subjects must meet the following criteria:

Be enrolled in 01-M-0254, The Evaluation of Participants with Mood and Anxiety Disorders and Healthy Volunteers or 17-M-0181, Recruitment and Characterization of Healthy Research Volunteers for NIMH Intramural Studies

Patients must meet the following criteria:

Exclusion Criteria

I do not have any untreated serious illnesses that would make joining unsafe.

I haven't taken NSAIDs, aspirin, corticosteroids (except for skin), or immunosuppressants like methotrexate in the last month.

I cannot travel to the NIH for treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Imaging

Participants undergo MRI and PET scans to measure COX-1 and COX-2 levels in the brain

1-2 days

2-5 visits (in-person)

Follow-up

Participants are monitored for any adverse effects and data is collected for analysis

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 11C-MC1
• 11C-PS13
• 18f-florbetaben

Trial Overview

The trial tests PET imaging agents (11C-MC1, 11C-PS13, 18f-florbetaben) to measure brain inflammation in neurodegenerative disorders versus healthy individuals. It involves MRI scans and two PET scans using these agents to compare COX enzyme levels between diseased and healthy brains.

How Is the Trial Designed?

Group I: Only one arm Experimental Treatment 3 Interventions

All subjects receive the same tests

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Florbetaben, an 18F-labeled PET tracer, has shown promising results in diagnosing Alzheimer's disease, with a sensitivity of 80% and specificity of 91% in distinguishing patients with probable AD from healthy controls in a recent multi-center trial.

Current research is focused on validating florbetaben's effectiveness by correlating PET imaging results with post-mortem evaluations and assessing its ability to predict progression to Alzheimer's in individuals with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Florbetaben to trace amyloid-β in the Alzheimer brain by means of PET. Barthel, H., Sabri, O.[2022]

Florbetaben, a novel β-amyloid PET tracer, was found to be safe and effective in distinguishing between patients with Alzheimer's disease (AD) and healthy controls, with 9 out of 10 AD patients showing β-amyloid positivity compared to only 1 out of 10 healthy controls.

The study demonstrated that the whole brain β-amyloid load derived from PET scans correlated significantly with cognitive decline, as measured by Mini-Mental State Examination scores, suggesting its potential as a surrogate marker for disease severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Individualized quantification of brain β-amyloid burden: results of a proof of mechanism phase 0 florbetaben PET trial in patients with Alzheimer's disease and healthy controls. Barthel, H., Luthardt, J., Becker, G., et al.[2022]

Positron emission tomography (PET) is a valuable tool for detecting early functional changes in the brain associated with Alzheimer's disease (AD), even before structural changes are visible on traditional imaging like MRI.

The review focuses on various (18)F- and (11)C-labelled PET tracers that can help in diagnosing AD early, understanding its pathophysiology, and monitoring treatment effects, highlighting their potential in improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiopharmaceuticals for positron emission tomography investigations of Alzheimer's disease. Någren, K., Halldin, C., Rinne, JO.[2021]

PET imaging with (18)F-AV-45 (florbetapir) effectively differentiates between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) from healthy controls, showing significant differences in amyloid load, particularly in the overall cortex.

The quantitative assessment of PET scans demonstrated high sensitivity (92.3%) and specificity (90.5%) for identifying AD, indicating that florbetapir is a promising and safe biomarker for routine clinical use, although visual assessments need improvement for better specificity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using PET with 18F-AV-45 (florbetapir) to quantify brain amyloid load in a clinical environment. Camus, V., Payoux, P., Barré, L., et al.[2022]

Current PET imaging techniques, particularly 18-fluorodeoxyglucose (FDG-PET), effectively measure brain metabolism and neuronal function in Alzheimer's disease, revealing distinct patterns of hypometabolism even before dementia symptoms appear.

While FDG-PET is widely used, novel PET approaches for imaging amyloid-beta plaques are already in clinical use, and efforts to develop tau imaging are ongoing, though challenges remain due to the nature of tau protein deposition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Brain Metabolism and Pathology in Alzheimer's Disease with Positron Emission Tomography. Shokouhi, S., Claassen, D., Riddle, W.[2020]

In a multicenter study involving 150 participants (81 with probable Alzheimer's disease and 69 healthy controls), florbetaben (¹⁸F) PET demonstrated a sensitivity of 80% and specificity of 91% in distinguishing Alzheimer's patients from healthy individuals based on amyloid-β accumulation in the brain.

The study found that florbetaben PET scans correlated well with cognitive impairment scores, indicating its potential as a reliable diagnostic tool for Alzheimer's disease without any noted safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebral amyloid-β PET with florbetaben (18F) in patients with Alzheimer's disease and healthy controls: a multicentre phase 2 diagnostic study. Barthel, H., Gertz, HJ., Dresel, S., et al.[2022]

Florbetaben is an FDA and EMA-approved PET tracer that effectively visualizes β-amyloid plaques in the brains of Alzheimer's disease patients, demonstrating its safety and efficacy through extensive clinical testing across multiple phases.

The tracer not only sensitively detects β-amyloid neuritic plaques but also has the potential to predict Alzheimer's dementia in individuals with mild cognitive impairment, making it a valuable tool for clinical diagnosis and differential diagnosis of dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beta-amyloid imaging with florbetaben. Sabri, O., Seibyl, J., Rowe, C., et al.[2022]

[(18)F]florbetaben is a highly accurate PET imaging agent that effectively detects β-amyloid plaques in the brain, demonstrating high sensitivity and specificity in identifying Alzheimer's disease and other cognitive impairments based on a phase III study.

The agent is generally well tolerated, with only mild to moderate adverse reactions reported, primarily related to the injection site, and no serious adverse events associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[(18)F]Florbetaben: a review in β-amyloid PET imaging in cognitive impairment. Syed, YY., Deeks, E.[2022]

In a study of 107 patients with suspected dementia, the use of [18F]-florbetaben (FBB)-PET significantly improved diagnostic clarity, allowing a final diagnosis to be established in 83% of previously unclear cases.

FBB-PET was particularly effective in differentiating Alzheimer's dementia from fronto-temporal dementia, changing the most likely diagnosis in 41% of cases, which is crucial for guiding future treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Additive value of amyloid-PET in routine cases of clinical dementia work-up after FDG-PET. Brendel, M., Schnabel, J., Schönecker, S., et al.[2018]

Early-phase [18F]-florbetaben (FBB) PET scans show strong correlation with [18F]-fluorodeoxyglucose (FDG) PET scans in assessing brain metabolism, suggesting that early FBB acquisitions can effectively indicate synaptic dysfunction in dementia diagnosis.

The study involved 33 patients and found that early-phase FBB imaging could potentially replace the need for additional FDG PET scans, as it provides similar diagnostic information regarding Alzheimer's disease without requiring later imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of early-phase [18F]-florbetaben PET acquisition in clinical routine cases. Daerr, S., Brendel, M., Zach, C., et al.[2022]

The novel compound [18F] JNJ-64326067 shows promise for detecting tau aggregates in the brain, with significant retention observed in 4 out of 5 participants with probable Alzheimer's disease, indicating its potential efficacy in identifying neurodegenerative changes.

The dosimetry results suggest that [18F] JNJ-64326067 has a low effective dose for both males and females, making it a safe option for imaging tau pathology in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evaluation of [18F] JNJ-64326067, a novel candidate PET tracer for the detection of tau pathology in Alzheimer's disease. Schmidt, ME., Janssens, L., Moechars, D., et al.[2021]

The production of [18F] AV-45 for PET imaging of Alzheimer's disease is efficient and reliable, with an average synthesis time of 52 minutes and a high radiochemical purity of over 95%.

PET/CT imaging using [18F] AV-45 showed significantly increased uptake in specific brain regions of Alzheimer's patients, particularly in the posterior cingulate gyrus, indicating its potential as a diagnostic tool for evaluating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Simple Synthesis of [18F] AV-45 and its Clinical Application in the Diagnosis of Alzheimer's Disease. Zhang, QZ., Yilihamu, N., Li, YB., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9537554/

Novel brain PET imaging agents - PubMed Central

Comparison of early-phase 11C-Deuterium-l-Deprenyl and 11C-Pittsburgh compound b PET for assessing brain perfusion in Alzheimer disease. J Nucl Med (2016) ...

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04396873

NCT04396873 | PET Imaging of Cyclooxygenases in ...

Primary Objective: To determine whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy ...

3.

jnm.snmjournals.org

jnm.snmjournals.org/content/64/supplement_1/P87

PET measurement of cyclooxygenase-2 (COX-2) with 11C ...

In transgenic mice, about 70-90% of 11C-MC1 uptake in brain could be blocked, thus confirming that 11C-MC1 specifically binds to the human receptor. Conclusions ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8198977/

Progress in PET Imaging of Neuroinflammation Targeting ...

This report indicates that [11C]MC1 may be a potential radioligand to image and quantify COX-2 upregulation in the brain during ...

5.

technologynetworks.com

technologynetworks.com/neuroscience/news/first-in-human-pet-imaging-technique-quantifies-brain-inflammation-397855

New PET Imaging Method Quantifies COX-2 in the Brain

A novel PET imaging method, using the radiotracer 11C-MC1, successfully quantifies COX-2 enzyme levels in the human brain.

6.

jnm.snmjournals.org

jnm.snmjournals.org/content/63/Supplement_1/53S

Cyclooxygenases as Potential PET Imaging Biomarkers to ...

This article reviews the development of PET radioligands for cyclooxygenase (COX) subtypes 1 and 2, enzymes that catalyze the production of inflammatory ...

7.

pubs.acs.org

pubs.acs.org/doi/10.1021/acscentsci.3c01564

A Fast-Binding, Functionally Reversible, COX-2 Radiotracer ...

This study introduces [ 11 C]BRD1158, which is a potent and uniquely fast-binding, selective COX-2 PET radiotracer.