[68Ga]CBP8 PET/MRI Imaging for Cardiac Amyloidosis

Recruiting in Palo Alto (17 mi)

Overseen by Sharmila Dorbala, MBBS, MPH

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Brigham and Women's Hospital

Disqualifiers: Dialysis, NYHA Class IV, others

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The primary aim of our pilot study is to determine whether fibrosis in the heart can be measured with \[68Ga\]CBP8, a positron emission tomography (PET) probe, using PET/magnetic resonance imaging (MRI) imaging, in 30 individuals with documented cardiac amyloidosis. The investigators will also enroll 15 individuals with recent myocardial infarction and 15 individuals with hypertrophic cardiomyopathy as positive controls for fibrosis, and the investigators will enroll 5 individuals without cardiovascular disease to undergo \[68Ga\]CBP8 PET/MRI imaging as a healthy control group. The primary hypothesis of this study is that \[68Ga\]CBP8 will bind to interstitial collagen and quantify myocardial fibrosis in patients with cardiac amyloidosis. The investigators hypothesize that \[68Ga\]CBP8 uptake will be greater in patients with cardiac amyloidosis, myocardial fibrosis, and hypertrophic cardiomyopathy than in healthy controls. Secondly, the investigators also hypothesize that \[68Ga\]CBP8 activity more strongly correlates with standard MRI measures in patients with recent myocardial infarction and hypertrophic cardiomyopathy (where extracellular expansion is caused by myocardial fibrosis/collagen deposition) than in patients with cardiac amyloidosis (where myocardial fibrosis is combined with infiltration).

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 study team or your doctor.

What data supports the effectiveness of the treatment [68Ga]CBP8 PET/MRI for cardiac amyloidosis?

Molecular imaging, like PET scans, is shown to be a sensitive tool for early assessment of cardiac amyloidosis, helping to differentiate between subtypes and monitor disease progression and response to therapy. This suggests that [68Ga]CBP8 PET/MRI could be effective in providing detailed images to aid in the diagnosis and management of cardiac amyloidosis. ^{1 2 3 4 5}

How is the treatment [68Ga]CBP8 PET/MRI different from other treatments for cardiac amyloidosis?

[68Ga]CBP8 PET/MRI is unique because it combines PET imaging with MRI to provide detailed images of the heart, potentially allowing for earlier and more accurate detection of cardiac amyloidosis compared to traditional imaging methods. This approach may help in identifying the disease at an early stage, which is crucial for timely treatment. ^{1 2 5 6 7}

Eligibility Criteria

This trial is for adults over 18 with cardiac amyloidosis, recent myocardial infarction, or hypertrophic cardiomyopathy. Healthy adults can also join as controls. Exclusions include pregnancy, severe claustrophobia, weight over MRI limit, heart failure that prevents lying flat, NYHA Class IV status, and certain contraindications to MRI.

Inclusion Criteria

I am over 18, can consent, and have AL amyloidosis with heart involvement.

I am over 18, agree to participate, and have been diagnosed with hypertrophic cardiomyopathy with MRI proof.

I am over 18, can consent, and have been diagnosed with a type of heart amyloidosis.

Exclusion Criteria

You weigh more than 300 pounds and cannot fit on the MRI table.

Any other reason determined by the investigator to be unsuitable for the study

You have had a bad reaction or allergy to gadolinium contrast dye in the past.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging

Participants undergo [68Ga]CBP8 PET/MRI imaging to measure myocardial fibrosis

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging

4 weeks

Treatment Details

Interventions

• [68Ga]CBP8 PET/MRI (Molecular Imaging Probe)

Trial Overview [68Ga]CBP8 PET/MRI imaging is being tested to see if it can measure heart fibrosis in patients with cardiac amyloidosis compared to those with other heart conditions and healthy individuals. The study aims to prove [68Ga]CBP8's effectiveness in binding interstitial collagen.

Participant Groups

Group I: [68Ga]CBP8 PET/MRI Amyloid Subjects Experimental Treatment 1 Intervention

Individuals with documented cardiac amyloidosis will undergo \[68Ga\]CBP8 PET/MRI.

Group II: [68Ga]CBP8 PET/MRI Recent Myocardial Infarction Subjects Active Control 1 Intervention

Individuals with recent myocardial infarction will undergo \[68Ga\]CBP8 PET/MRI.

Group III: [68Ga]CBP8 PET/MRI Hypertrophic Cardiomyopathy Subjects Active Control 1 Intervention

Individuals with hypertrophic cardiomyopathy will undergo \[68Ga\]CBP8 PET/MRI.

Group IV: [68Ga]CBP8 PET/MRI Healthy Controls Placebo Group 1 Intervention

Individuals without documented cardiovascular disease will undergo \[68Ga\]CBP8 PET/MRI.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Brigham and Women's Hospital Boston, MA

Who Is Running the Clinical Trial?

Brigham and Women's Hospital Lead Sponsor

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis. [2021] Background: Cardiac amyloidosis is an increasingly recognized etiology of heart failure, in part due to the rise of non-invasive nuclear bone scintigraphy. Molecular imaging using positron emission tomography (PET) has promised the direct visualization of cardiac amyloid fibrils. We sought to assess the performance of F18-florbetapir PET in patients with a potential for cardiac amyloidosis in order to identify early disease. Methods: We performed a pilot study of 12 patients: one with asymptomatic transthyretin cardiac amyloidosis, seven with a potential for developing cardiac amyloidosis (two smoldering myeloma and five with extracardiac biopsy demonstrating transthyretin amyloid deposits and negative technetium pyrophosphate scans), and four controls. Patients were imaged with PET/CT in listmode 10-20 min after receiving F18-florbetapir. Static images were created from this acquisition, and mean standardized uptake values (SUVs) of the left ventricular myocardium, blood pool, paraspinal muscles, and liver were calculated. Results: All 12 patients demonstrated radiotracer uptake in the myocardium with mean SUV of 2.3 ± 0.4 and blood pool SUV of 0.8 ± 0.1. The patient with cardiac amyloidosis had SUV of 3.3, while mean SUV for patients at risk was 2.3 ± 0.4 and for controls was 2.2 ± 0.3. After 3 years of follow-up, one patient with SUV below the mean was subsequently diagnosed with ATTR cardiac amyloidosis. Conclusion: In this cohort, PET with F18-florbetapir demonstrated non-specific radiotracer uptake in the myocardium in all patients using a static image protocol; though, the highest values were noted in a patient with ATTR cardiac amyloidosis. There was no difference in the intensity of F18-florbetapir uptake in at-risk patients and controls. Future studies should continue to investigate metabolic PET tracers and protocols in cardiac amyloidosis, including in early disease.

2. United Arab Emirates pubmed.ncbi.nlm.nih.gov

The Role of Molecular Imaging in the Assessment of Cardiac Amyloidosis: State-of-the-Art. [2021] Cardiac amyloidosis is a progressive infiltrative disease for which new treatments are now available. As therapy should be started as early as possible to avoid complications such as restrictive cardiomyopathy, arrhythmias and heart failure, a prompt and reliable diagnosis by means of non-invasive tests would be highly warranted. Electrocardiography, echocardiography and cardiac magnetic resonance imaging are all used in the evaluation of cardiac amyloidosis with varying diagnostic and prognostic accuracy, but none of these modalities can effectively differentiate the cardiac amyloid subtypes. We aim to highlight the most relevant findings in the literature of molecular imaging in the assessment of patients with cardiac amyloidosis and to underline future clinical perspective. We performed multiple searches using Pub-Med databases in order to find important original articles on the role of molecular imaging in the assessment of patients affected by CA. Several search terms were used, such as "cardiac amyloidosis"; "Light-chain amyloidosis"; "Transthyretin amyloid cardiomyopathy"; "bone scintigraphy"; "single photon emission tomography" or "SPECT"; "Positron emission tomography or PET", and "cardiac imaging". All radiopharmaceuticals tracing cardiac amyloidosis were also included. Several studies about the role of SPECT with bone-seeking tracer (47 articles) and innervation tracer (9 articles) in the work-up of CA, as well as new PET amyloid-binding (14 articles) and bone radiotracer (4 articles) have been reviewed and discussed. Molecular imaging represents a sensitive tool for early assessment of both amyloid burden and cardiac innervation, to differentiate between subtypes and to monitor disease burden, disease progression, and potential response to therapy.

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

Comparison between (99m)Tc-diphosphonate imaging and MRI with late gadolinium enhancement in evaluating cardiac involvement in patients with transthyretin familial amyloid polyneuropathy. [2015] Cardiac involvement is not rare in systemic amyloidosis and is associated with poor prognosis. Both (99m)Tc-diphosphonate imaging and cardiac MRI with late gadolinium enhancement are considered valuable tools in revealing amyloid deposition in the myocardium; however, to our knowledge, no comparative study between the two techniques exists. We compared findings of these two techniques in patients with transthyretin-familial amyloid polyneuropathy (FAP).

4. Germany pubmed.ncbi.nlm.nih.gov

Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy. [2020] Label="PURPOSE" NlmCategory="OBJECTIVE">Cardiac amyloidosis (CA) is a rare cause of heart failure with frequently delayed diagnosis, because specific early signs or symptoms are missing. Recently, direct amyloid imaging using positron emission tomography/computed tomography (PET/CT) has emerged. The aim of this study was to examine the performance of 18F-florbetaben-PET/CT in detection of CA, and compare it to echocardiography (echo), cardiac MRI (CMR) and scintigraphy. Additionally, the use of 18F-florbetaben-PET/CT for quantification of amyloid burden and monitoring of treatment response was assessed.

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

18F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis. [2022] Label="BACKGROUND" NlmCategory="BACKGROUND">We evaluated the diagnostic performance of 18F-NaF PET/MRI in patients with suspected cardiac amyloidosis (CA).

6. Switzerland pubmed.ncbi.nlm.nih.gov

Diagnostic Value of 11C-PIB PET/MR in Cardiac Amyloidosis. [2022] Label="Background" NlmCategory="UNASSIGNED">The thioflavin T derivative, 11C-Pittsburgh-B (PIB), is used for Alzheimer's disease imaging because it specifically binds to β-amyloid protein deposits in the brain. The aim of this study was to estimate the diagnostic value of combined 11C-PIB positron emission tomography/magnetic resonance (PET/MR) in cardiac amyloidosis (CA).

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

Cardiac Amyloid Imaging with 18F-Florbetaben PET: A Pilot Study. [2017] Our aim was to determine the feasibility of 18F-florbetaben PET in diagnosing cardiac amyloidosis.