64Cu-FBP8 PET Scan for Alzheimer's Disease

Overseen By Ciprian Catana, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Massachusetts General Hospital

Disqualifiers: Seizures, Claustrophobia, Cardiac arrest, others

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

Compensation: Varies

Number of Visits: 1

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new brain scanning method using 64Cu-FBP8, an imaging agent, to measure fibrin, a type of protein, in individuals with and without Alzheimer's Disease. Researchers aim to identify differences in fibrin levels across various brain regions. The trial seeks participants aged 55 to 90 who can consent to participate, including healthy individuals and those diagnosed with Alzheimer's or similar conditions. As a Phase 1 trial, this research focuses on understanding how the new imaging agent functions in people, offering participants the chance to contribute to groundbreaking advancements in Alzheimer's research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that 64Cu-FBP8 PET/MR Imaging is safe for use in humans?

Research shows that 64Cu-FBP8 has been tested for safety in animals and is now under study in humans. Earlier studies found that 64Cu-FBP8 has low radiation levels, a positive sign for safety. It also exits the bloodstream quickly and is removed through the kidneys, reducing the chance of side effects.

Although the FDA has not yet approved 64Cu-FBP8, early studies suggest it is well-tolerated, with no serious negative effects reported so far. In studies conducted to date, participants did not experience significant harmful effects. As testing continues, researchers will closely monitor safety to ensure it remains a good option for participants. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike standard Alzheimer's treatments that primarily focus on managing symptoms, 64Cu-FBP8 PET scans offer a different approach by aiming to improve the diagnosis of the disease. Researchers are excited about this technique because it uses the radioactive tracer 64Cu-FBP8, which targets fibrin in the brain. This could help detect Alzheimer’s-related changes much earlier and more accurately than current methods. By potentially providing clearer images of brain activity, this PET scan might lead to better understanding and monitoring of Alzheimer’s progression.

What evidence suggests that 64Cu-FBP8 PET Scan is effective for Alzheimer's Disease?

Research has shown that 64Cu-FBP8, which participants in this trial will receive, is a promising tool for detecting fibrin in the brain. Fibrin, a protein related to blood clots, has been linked to Alzheimer's disease. Studies have demonstrated that this probe effectively highlights fibrin in conditions like deep vein thrombosis and pulmonary embolism in animals. Early findings suggest that 64Cu-FBP8 could help visualize fibrin buildup in the brain, potentially providing insights into Alzheimer's disease. Although data in humans is limited, the probe's ability to target fibrin makes it a strong candidate for further Alzheimer's research. ^{1 2 4 5 6}

Who Is on the Research Team?

Ciprian Catana, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 55-90 with Alzheimer's Disease or dementia, who can consent to participate. Healthy volunteers must have no history of these conditions. Participants should not have metal implants, be at risk for seizures or claustrophobia, and must not exceed radiation exposure limits.

Inclusion Criteria

Ability to provide informed consent

I am between 55 and 90 years old.

Healthy volunteers: no history of ADRD

Exclusion Criteria

My kidney function is good enough for a specific MRI contrast.

I do not have conditions that increase my risk of seizures, claustrophobia, or cardiac arrest.

MR contraindications such as electrical implants such as cardiac pacemakers or perfusion pumps, ferromagnetic implants such as aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants, ferromagnetic objects such as jewelry or metal clips in clothing

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo 64Cu-FBP8-PET imaging to quantify brain fibrin content

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 64Cu-FBP8
• PET/MR Imaging

Trial Overview

The study uses a special PET/MR imaging technique with a tracer called 64Cu-FBP8 to measure the amount of fibrin in the brain, which could help understand differences in brain regions affected by Alzheimer's Disease and related dementias.

How Is the Trial Designed?

Group I: Cognitively Normal Subjects and ADRD subjects Experimental Treatment 2 Interventions

Cognitively Normal Subjects and ADRD subjects

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The novel PET probe (64)Cu-FBP8 effectively detects deep vein thrombosis (DVT) and pulmonary embolism (PE) in rats, showing significant differences in uptake between thrombus and background tissues, which supports its potential use in clinical settings.

The biodistribution studies indicate that (64)Cu-FBP8 has a rapid clearance from the body, with low radiation exposure (0.021 mSv/MBq for males and 0.027 mSv/MBq for females), making it a safe option for human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiation Dosimetry of the Fibrin-Binding Probe ⁶⁴Cu-FBP8 and Its Feasibility for PET Imaging of Deep Vein Thrombosis and Pulmonary Embolism in Rats. Blasi, F., Oliveira, BL., Rietz, TA., et al.[2018]

Two novel PET imaging probes labeled with (64)Cu were developed to detect β-amyloid aggregates associated with Alzheimer's disease, showing promising binding affinity for Aβ(1-42) aggregates in vitro.

While these probes demonstrated feasibility for Aβ imaging, they exhibited low brain uptake in normal mice, indicating that further refinement is necessary to improve their effectiveness for clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting β-amyloid aggregates. Watanabe, H., Kawasaki, A., Sano, K., et al.[2017]

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]

The 64Cu PET imaging agent developed shows significant ability to penetrate the blood-brain barrier and specifically bind to beta-amyloid aggregates, which are associated with Alzheimer's disease.

This imaging agent successfully differentiates between amyloid plaque presence in the brains of 5xFAD mice and wild-type mice, indicating its potential for effective in vivo imaging of Alzheimer's pathology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease. Cho, HJ., Huynh, TT., Rogers, BE., et al.[2021]

The study involved 61 healthy volunteers and 55 patients with suspected dementia, demonstrating that the new PET tracer 18F-FPYBF-2 effectively detects β-amyloid plaques in Alzheimer's Disease, with significantly higher uptake in patients compared to healthy individuals.

Comparative analysis with the established tracer 11C-Pittsburgh Compound B showed that 18F-FPYBF-2 provides comparable results, indicating its potential as a reliable diagnostic tool for evaluating β-amyloid deposition in dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-FPYBF-2, a new F-18-labelled amyloid imaging PET tracer: first experience in 61 volunteers and 55 patients with dementia. Higashi, T., Nishii, R., Kagawa, S., et al.[2020]

The tracer (18)F-FDDNP shows low cortical uptake in Alzheimer's disease due to its weak binding affinity for neurofibrillary tangles and senile plaques, as demonstrated by binding assays with brain sections and comparison to (3)H-PIB.

In contrast, (3)H-PIB exhibited strong binding to various forms of amyloid pathology, indicating that (18)F-FDDNP may not be as effective for imaging Alzheimer's disease compared to other tracers like (3)H-PIB.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer's disease pathologies. Thompson, PW., Ye, L., Morgenstern, JL., et al.[2022]

Pittsburgh compound-B (PiB) is a highly validated PET imaging tracer that specifically binds to fibrillar β-amyloid deposits in the brain, making it a reliable marker for detecting early amyloid deposition associated with dementia.

PiB-PET imaging can identify healthy individuals and those with mild cognitive impairment who are at high risk for developing Alzheimer's disease, potentially allowing for early intervention and preventive measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular neuroimaging in Alzheimer's disease. Matsuda, H., Imabayashi, E.[2016]

In a study comparing two PET imaging agents, PIB and FDDNP, in two brothers with a genetic mutation linked to prion disease, PIB showed normal uptake while FDDNP indicated intermediate levels between healthy controls and Alzheimer's patients, suggesting different sensitivities to prion-related brain changes.

These findings imply that using a combination of amyloid-binding agents like PIB and FDDNP could enhance the diagnosis of early-onset dementia, particularly in cases that resemble Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease. Boxer, AL., Rabinovici, GD., Kepe, V., et al.[2016]

FPYBF-1 is a promising PET imaging probe that shows high affinity for β-amyloid plaques associated with Alzheimer's disease, demonstrating a binding affinity of 0.9 nM in vitro.

In vivo studies in a murine model of Alzheimer's disease showed that [(18)F]FPYBF-1 has good initial brain uptake and specific labeling of β-amyloid plaques, indicating its potential for imaging these plaques in living brain tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel 18F-labeled pyridyl benzofuran derivative for imaging of β-amyloid plaques in Alzheimer's brains. Cheng, Y., Ono, M., Kimura, H., et al.[2016]

Three new fibrin-targeted PET probes (FBP1, FBP2, FBP3) were developed and evaluated for their ability to detect thrombi, showing high specificity and effectiveness in a rat model of carotid artery thrombosis.

FBP1 and FBP2 demonstrated significantly higher uptake in thrombus-containing arteries compared to the contralateral arteries, indicating their potential as effective tools for noninvasive thrombus imaging, confirmed by hybrid MR-PET imaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fibrin-targeted PET probes for the detection of thrombi. Ciesienski, KL., Yang, Y., Ay, I., et al.[2022]

Recent advancements in non-invasive molecular imaging techniques have shown promise in detecting thrombosis by targeting fibrin, a key component in thrombus formation, across various disease models and in patients.

The fibrin-binding PET probe [64Cu]FBP8 has successfully progressed from preclinical studies to human trials, highlighting its potential for improving the diagnosis and monitoring of thrombosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peptide-based fibrin-targeting probes for thrombus imaging. Oliveira, BL., Caravan, P.[2018]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11230308/

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe

This study presents the biodistribution, clearance and dosimetry estimates of [64Cu]Fibrin Binding Probe #8 ([64Cu]FBP8) in healthy subjects.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05336695

NCT05336695 | Assess Fibrin in Brains With AD/ADRD

The goal of this project is to quantify brain fibrin content using 64Cu-FBP8-PET in the brains of subjects ranging from cognitively normal to clinically ...

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/39633070/

First-in-human Evaluation of Safety and Dosimetry of [64Cu ...

This study demonstrates the following properties of the [ 64 Cu]FBP8 probe: low dosimetry estimates; fast blood clearance and renal excretion; ...

4.

withpower.com

withpower.com/trial/phase-2-dementia-2-2022-0d6f7

64Cu-FBP8 PET Scan for Alzheimer's Disease

The novel PET probe (64)Cu-FBP8 effectively detects deep vein thrombosis (DVT) and pulmonary embolism (PE) in rats, showing significant differences in uptake ...

5.

trialfinder.panfoundation.org

trialfinder.panfoundation.org/en-US/trial/listing/370742

Assess Fibrin in Brains With AD/ADRD

The goal of this project is to quantify brain fibrin content using 64Cu-FBP8-PET in the brains of subjects ranging from cognitively normal ...

6.

jnm.snmjournals.org

jnm.snmjournals.org/content/56/7/1088

Radiation Dosimetry of the Fibrin-Binding Probe 64 Cu-FBP8 ...

We tested the feasibility of 64 Cu-FBP8 PET to detect source thrombi and culprit emboli after deep vein thrombosis and pulmonary embolism (DVT-PE).