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

Overseen By Sharmila Dorbala, MBBS, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Brigham and Women's Hospital

Disqualifiers: Dialysis, NYHA Class IV, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

65 Participants Needed

Trial Summary

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}

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).

Research Team

Sharmila Dorbala, MBBS, MPH

Principal Investigator

Brigham and Women's Hospital

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.

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.

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

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.

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

In a pilot study of 12 patients, F18-florbetapir PET imaging showed radiotracer uptake in the myocardium of all participants, indicating its potential for visualizing cardiac amyloid fibrils, although the uptake was non-specific.

The highest uptake values were observed in a patient already diagnosed with transthyretin cardiac amyloidosis, while at-risk patients and controls showed similar uptake levels, suggesting that further research is needed to refine PET imaging protocols for early detection of cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis. Sperry, BW., Bock, A., DiFilippo, FP., et al.[2021]

Molecular imaging techniques, such as SPECT and PET, are emerging as sensitive tools for the early assessment of cardiac amyloidosis, helping to differentiate between amyloid subtypes and monitor disease progression.

Prompt diagnosis using these advanced imaging methods is crucial for initiating treatment early, potentially preventing serious complications like restrictive cardiomyopathy and heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Molecular Imaging in the Assessment of Cardiac Amyloidosis: State-of-the-Art. Popescu, C., Burger, IA.[2021]

In a study of 18 patients with transthyretin-familial amyloid polyneuropathy, both (99m)Tc-diphosphonate imaging and cardiac MRI with late gadolinium enhancement were effective in detecting myocardial amyloid deposition, but (99m)Tc-diphosphonate imaging identified a greater extent of amyloid infiltration.

The findings suggest that while both imaging techniques are valuable, (99m)Tc-diphosphonate imaging may provide a more accurate assessment of cardiac amyloid burden compared to MRI, which could lead to underestimation of the condition.

NCBI (Pubmed)

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. Minutoli, F., Di Bella, G., Mazzeo, A., et al.[2015]

The study involving 22 patients demonstrated that 18F-florbetaben-PET/CT effectively detected cardiac amyloidosis (CA) in 14 out of 22 patients, providing a reliable diagnostic tool compared to traditional methods like echocardiography and cardiac MRI.

The imaging technique not only helped in identifying CA but also showed potential in quantifying amyloid burden and monitoring treatment response, with changes in myocardial tracer retention correlating well with clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of cardiac amyloidosis with 18F-Florbetaben-PET/CT in comparison to echocardiography, cardiac MRI and DPD-scintigraphy. Kircher, M., Ihne, S., Brumberg, J., et al.[2020]

In a study of 27 patients suspected of having cardiac amyloidosis, 18F-NaF PET/MRI demonstrated good diagnostic performance, particularly when using semi-quantitative measures like myocardium-to-blood pool (M/B) ratios to differentiate between types of cardiac amyloidosis.

The study found that M/B ratios were significantly higher in transthyretin (TTR) cardiac amyloidosis compared to light-chain (AL) and no cardiac amyloidosis, indicating that while 18F-NaF PET/MRI can effectively assess amyloid load, visual interpretation may be challenging in routine clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

18F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis. Abulizi, M., Sifaoui, I., Wuliya-Gariepy, M., et al.[2022]

The study demonstrated that 11C-PIB PET/MRI is highly effective for diagnosing cardiac amyloidosis (CA) in heart failure patients, achieving a diagnostic sensitivity of 92.3% and specificity of 100%.

Thirteen out of 23 heart failure patients were diagnosed with CA, and the imaging technique successfully distinguished CA patients from non-CA patients and healthy controls, indicating its potential as a non-invasive diagnostic tool.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnostic Value of 11C-PIB PET/MR in Cardiac Amyloidosis. Bi, X., Xu, B., Liu, J., et al.[2022]

18F-florbetaben PET imaging is effective in diagnosing cardiac amyloidosis, showing higher retention in amyloid patients compared to those with hypertensive heart disease, with a cutoff of 40% for differentiation.

The percentage of myocardial 18F-florbetaben retention is a key indicator of myocardial dysfunction in cardiac amyloidosis, correlating inversely with global left ventricular and right ventricular strain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Amyloid Imaging with 18F-Florbetaben PET: A Pilot Study. Law, WP., Wang, WY., Moore, PT., et al.[2017]

References

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

Pilot Study of F18-Florbetapir in the Early Evaluation of Cardiac Amyloidosis. [2021]

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]

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]

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]

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

18F-sodium fluoride PET/MRI myocardial imaging in patients with suspected cardiac amyloidosis. [2022]

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

Diagnostic Value of 11C-PIB PET/MR in Cardiac Amyloidosis. [2022]

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

Cardiac Amyloid Imaging with 18F-Florbetaben PET: A Pilot Study. [2017]