64Cu-FBP8 PET Scan for Alzheimer's Disease

Recruiting in Palo Alto (17 mi)

Overseen by Ciprian Catana, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

Sponsor: Massachusetts General Hospital

Disqualifiers: Seizures, Claustrophobia, Cardiac arrest, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial uses a special brain scan to detect certain protein levels in people ranging from normal cognitive function to those with Alzheimer's disease and related dementias. The scan helps researchers understand how these proteins are distributed in the brain.

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 data supports the effectiveness of the drug 64Cu-FBP8 for Alzheimer's disease?

Research shows that similar copper-64 labeled compounds have been effective in imaging beta-amyloid plaques, which are associated with Alzheimer's disease. These compounds have demonstrated the ability to bind to amyloid aggregates and successfully image plaques in animal models, suggesting potential for 64Cu-FBP8 in Alzheimer's imaging. ^{1 2 3 4 5}

Is 64Cu-FBP8 safe for use in humans?

The safety of 64Cu-FBP8 has been evaluated in animal studies, which are a step towards human trials. These studies help estimate how the body processes the compound, but specific human safety data is not provided in the available research. ^{1 6 7 8 9}

How is the drug 64Cu-FBP8 unique for Alzheimer's disease?

64Cu-FBP8 is a novel imaging agent used in PET scans to detect fibrin, which may help in understanding Alzheimer's disease differently from traditional amyloid imaging agents like PiB that focus on amyloid plaques. ^{4 9 10 11 12}

Research Team

Ciprian Catana, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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

Healthy volunteers: no history of ADRD

I am between 55 and 90 years old.

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

Trial Timeline

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

Treatment Details

Interventions

• 64Cu-FBP8 (Radiopharmaceutical)
• PET/MR Imaging (Diagnostic Test)

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.

Participant Groups

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+

Dr. William Curry

Massachusetts General Hospital

Chief Medical Officer

MD from Harvard Medical School

Dr. Anne Klibanski

Massachusetts General Hospital

Chief Executive Officer since 2019

MD from Harvard Medical School

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

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]

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]

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]

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]

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]

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 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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting β-amyloid aggregates. [2017]

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

Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease. [2021]

3. Japan 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. [2020]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

A novel 18F-labeled pyridyl benzofuran derivative for imaging of β-amyloid plaques in Alzheimer's brains. [2016]

6. United States 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. [2018]

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

Fibrin-targeted PET probes for the detection of thrombi. [2022]

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

Peptide-based fibrin-targeting probes for thrombus imaging. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Interaction of the amyloid imaging tracer FDDNP with hallmark Alzheimer's disease pathologies. [2022]

10. 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]

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

Molecular neuroimaging in Alzheimer's disease. [2016]

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

Amyloid imaging in distinguishing atypical prion disease from Alzheimer disease. [2016]