18F-mFBG Imaging for Cardiovascular Disease

Overseen By Robert Armenti, MS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Illumina Radiopharmaceuticals, LLC

Must not be taking: NET-interfering agents

Disqualifiers: Diabetes, Neurological disease, Renal insufficiency, others

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

Compensation: Varies

Number of Visits: 2

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging agent called 18F-mFBG to help doctors assess nerve function in the heart. It targets individuals with heart failure and those at low risk for heart disease. The goal is to enhance understanding of heart conditions using a specialized PET scan. Candidates may include those who have experienced heart failure for over a year with a specific heart function condition, or those who are generally healthy with a low risk of heart disease. Participation could provide insights into heart health through advanced imaging. As a Phase 1 and Phase 2 trial, this research aims to understand how the imaging agent works in people and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking heart health research.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that interfere with NET-dependent agents at least 24 hours before the study procedures.

What prior data suggests that 18F-mFBG is safe for imaging in cardiovascular disease?

Research has shown that 18F-mFBG, a special imaging drug, has been tested for its safety and effectiveness in assessing heart health. Studies have found that most patients tolerate this imaging drug well. Past studies have reported no major adverse reactions directly linked to 18F-mFBG, suggesting it is likely safe for imaging purposes.

As this study is in its early stages, it primarily focuses on evaluating the safety of 18F-mFBG and the body's response to it. This phase of the research closely monitors participants for any side effects, ensuring the treatment is safe for further testing. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the 18F-mFBG imaging technique for cardiovascular disease because it offers a novel way to assess heart health by visualizing myocardial sympathetic innervation. Unlike traditional imaging methods that primarily focus on structural aspects of the heart, 18F-mFBG provides insights into the sympathetic nervous system’s role in heart function, which could lead to earlier and more precise diagnoses. This approach could be particularly transformative for patients with heart failure or those at low risk for coronary heart disease, as it allows for comprehensive imaging of the heart and body, potentially unveiling factors that existing methods might miss.

What evidence suggests that 18F-mFBG is effective for cardiovascular disease imaging?

This trial will evaluate 18F-mFBG as an imaging tool for examining nerve activity in the heart. Studies have shown that 18F-mFBG provides clearer and more detailed images than traditional methods like [123I]mIBG, allowing for better visualization of the heart's nerve activity. Initial findings suggest that 18F-mFBG can help identify different types of heart conditions by highlighting patterns in nerve activity. Overall, 18F-mFBG shows promise as a powerful tool for evaluating heart health. Participants in this trial will be divided into two groups: those with heart failure and left ventricular function (LVEF ≤ 35%) and those with a low likelihood of coronary heart disease, to assess the imaging's effectiveness in different conditions. ^{1 5 6 7 8}

Who Is on the Research Team?

Vikram Agarwal, MD

Principal Investigator

Mount Sinai Morningside

Are You a Good Fit for This Trial?

This trial is for adults who can follow the study procedures and have signed a consent form. It's open to those who are sterile, postmenopausal, not breastfeeding, or if of childbearing potential, not pregnant. People with recent heart procedures, serious allergies to the imaging agent, certain pacemakers, high plasma catecholamines due to non-cardiac conditions like pheochromocytoma, claustrophobia preventing stillness during scans, severe kidney issues or on interfering medications cannot join.

Inclusion Criteria

able and willing to comply with study procedures

signed and dated informed consent is obtained

male or a female who is either surgically sterile (has had a documented bilateral oophorectomy and/or hysterectomy), postmenopausal (cessation of menses for more than 1 year), non-lactating, or of childbearing potential for whom the result of a serum pregnancy test performed at screening is negative.

Exclusion Criteria

Ventricular pacemaker that routinely functions (>5% paced beats)

Cardiac revascularization (e.g., percutaneous transluminal coronary angioplasty, PCI, or CABG), or an acute myocardial infarction within the past 30 days.

Serious non-cardiac medical condition associated with significant elevation of plasma catecholamines including pheochromocytoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Imaging Procedure - Control Group

Control subjects with low likelihood of coronary heart disease undergo thorax and total body imaging for quantification of myocardial sympathetic innervation.

210 minutes

1 visit (in-person)

Imaging Procedure - Heart Failure Group

Patients with NYHA class 2 heart failure and reduced LV systolic function undergo thorax and total body imaging for quantification of myocardial sympathetic innervation.

100 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after imaging procedures

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 18F-mFBG

Trial Overview The study tests an injectable radiopharmaceutical called 18F-mFBG as an imaging tool for measuring nerve activity in the heart muscle. This early-phase trial aims to see how well it works and will involve participants receiving an injection followed by detailed heart scans.

How Is the Trial Designed?

Group I: Low likelihood of coronary heart disease Experimental Treatment 1 Intervention

Thorax and total body imaging for quantification of normal biodistribution and myocardial sympathetic innervation. PET imaging to 210 minutes post-administration.

Group II: Heart Failure + left ventricular function (LVEF ≤ 35%) Experimental Treatment 1 Intervention

Thorax and total body imaging for quantification of myocardial sympathetic innervation. PET imaging to 100 minutes post-administration

Who Is Running the Clinical Trial?

Illumina Radiopharmaceuticals, LLC

Lead Sponsor

Trials

2

Recruited

60+

Innervate Radiopharmaceuticals LLC (Formerly: Illumina Radiopharmaceuticals LLC)

Lead Sponsor

Trials

3

Recruited

60+

Mount Sinai Hospital, New York

Collaborator

Trials

37

Recruited

892,000+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Cardiac sympathetic imaging using meta-iodobenzylguanidine (mIBG) is a noninvasive method that effectively predicts survival in patients with heart failure, regardless of whether they have ischemic or nonischemic cardiomyopathy.

This imaging technique helps to clarify the harmful effects of sympathetic overactivity in heart failure, potentially leading to improved treatment strategies and outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac sympathetic imaging with mIBG in heart failure. Carrió, I., Cowie, MR., Yamazaki, J., et al.[2016]

A meta-analysis of seven studies involving 1357 patients with heart failure showed that low late heart-to-mediastinum (H/M) ratios from ¹²³I-MIBG imaging significantly indicate a higher risk of cardiac death, with a pooled odds ratio of 5.2.

Increased washout rates of ¹²³I-MIBG were also linked to a higher risk of lethal events, with a pooled odds ratio of 2.8, although this association showed more variability among studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of the survival rate in patients with congestive heart failure stratified by ¹²³I-MIBG imaging: a meta-analysis from the studies performed in Japan. Kuwabara, Y., Tamaki, N., Nakata, T., et al.[2016]

The study demonstrated that the F-18-labeled mIBG derivative, [18F]mFPBG, provides improved spatial resolution and sensitivity in cardiac imaging compared to the traditional [123I]mIBG, making it more effective for assessing ischemic and viable myocardium in a rat model of myocardial infarction.

Infarct size measurements obtained through [18F]mFPBG PET imaging closely matched histological findings, indicating its reliability and potential as a diagnostic tool in PET cardiology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of myocardial PET imaging using a benzylguanidine analog: meta-(3-[18F]fluoropropyl)benzylguanidine ([18F]mFPBG). Woo, SK., Moon, BS., Kim, BS., et al.[2019]

In a study of 22 patients with dilated cardiomyopathy (DCM), T2 mapping showed lower values in patients who responded to treatment (increased left ventricular ejection fraction) compared to non-responders, suggesting it may be a useful tool for assessing cardiac function.

The study found a significant correlation between T2 values and MIBG scintigraphy indices, indicating that both imaging techniques can provide valuable insights into heart failure severity and potential recovery in DCM patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparison of Quantitative T2 Mapping on Cardiovascular Magnetic Resonance Imaging with Metaiodobenzylguanidine Scintigraphy and Left Ventricular Functional Recovery in Dilated Cardiomyopathy: A Retrospective Pilot Study. Ito, T., K Kono, A., Takamine, S., et al.[2018]

Iodine-123-meta-iodobenzyl-guanidine (MIBG) scintigraphy is effective in evaluating the impact of pharmacological treatments on cardiac sympathetic neuronal function in heart failure patients, based on a review of 33 studies involving 1124 patients.

The study highlights that MIBG scintigraphy can successfully assess changes in myocardial innervation, providing valuable insights into the effectiveness of various heart failure treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical usefulness of myocardial innervation imaging using Iodine-123-meta-iodobenzylguanidine scintigraphy in evaluating the effectiveness of pharmacological treatments in patients with heart failure: an overview. Treglia, G., Stefanelli, A., Bruno, I., et al.[2016]

The study demonstrated that [18F]PFBG is effectively taken up by sympathetic nerve terminals in the heart, with significant reductions in uptake observed when specific uptake mechanisms were blocked, indicating its potential as a tracer for imaging myocardial sympathetic innervation.

The research identified distinct mechanisms of uptake and clearance for [18F]PFBG, including rapid and slow clearance phases, and suggested that reverse transport through the uptake-1 carrier may play a role in its retention, warranting further investigation in human subjects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart. Berry, CR., Garg, PK., Zalutsky, MR., et al.[2016]

In a study of 290 heart failure patients, a lower heart-to-mediastinum (H/M) ratio from (123)I-mIBG scans was significantly associated with higher rates of major cardiac events (MCEs), indicating its prognostic value in assessing risk.

Using an H/M ratio threshold of 1.75, patients with a ratio below this had a 62% event-free survival rate over two years, compared to 95% for those above the threshold, highlighting its potential as a predictive marker for cardiac mortality and arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

I-123-mIBG myocardial imaging for assessment of risk for a major cardiac event in heart failure patients: insights from a retrospective European multicenter study. Agostini, D., Verberne, HJ., Burchert, W., et al.[2022]

18F-FDG and 18F-NaF are commonly used PET tracers but have limitations in effectively imaging heart diseases.

Recent studies suggest that alternative radiotracers may offer better identification and monitoring of cardiovascular diseases, indicating a need for further research to establish their clinical value.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-18F-FDG/18F-NaF Radiotracers Proposed for the Diagnosis and Management of Diseases of the Heart and Vasculature. Hancin, EC., Raynor, WY., Borja, AJ., et al.[2021]

In a randomized trial involving 430 patients with severe left ventricular dysfunction and suspected coronary disease, FDG PET-assisted management did not show a significant overall reduction in cardiac events compared to standard care, with 30% of the PET group experiencing adverse events versus 36% in the standard care group.

However, patients who followed PET recommendations for revascularization showed a significant reduction in cardiac events, particularly in those without recent angiography, indicating that FDG PET may be most beneficial when its recommendations are adhered to.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease: a randomized, controlled trial (PARR-2). Beanlands, RS., Nichol, G., Huszti, E., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06965621?lastUpdPost=2020-10-10_

18F-mFBG Imaging for Myocardial Sympathetic Innervation The study will examine a group of stable patients with heart failure (HF) from ischemic cardiomyopathy. All subjects will have left ventricular ejection ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34993893/

F-18 meta-fluorobenzylguanidine PET imaging of myocardial ... MFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation.

3. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/252135

Evaluating the Efficacy of 18F-MFBG PET/CT in Differentiating ... Conclusions: 18F-MFBG PET/CT is an effective imaging modality for assessing myocardial sympathetic innervation, facilitating the differential ...

4. withpower.com withpower.com/trial/phase-2-cardiovascular-diseases-8-2021-38029

18F-mFBG Imaging for Cardiovascular Disease 18F-mFBG is a novel imaging agent that offers higher spatial resolution and sensitivity compared to the traditional [123I]mIBG imaging used for assessing ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10155237/

F-18 meta-fluorobenzylguanidine PET imaging ... MFBG is a promising PET radiotracer for the assessment of myocardial sympathetic innervation. Keywords: MFBG, Dynamic PET, Pharmacokinetic modeling, Heart ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S107135812300658X

F-18 meta-fluorobenzylguanidine PET imaging of ... This study provides knowledge about how a novel PET tracer MFBG may be useful in imaging the sympathetic innervation of the heart.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02348749

Study Details | NCT02348749 | 18F-MFBG Imaging for ... The purpose of this study is to see how a new tracer named 18F-MFBG (Meta Fluorobenzyl Guanidine) behaves in the body after injection, how it spreads to all ...

8. onlinecjc.ca onlinecjc.ca/article/S0828-282X(25)00471-4/abstract

PET Imaging of Cardiac SNS Function with [18F]mFBG in ... We predicted use of [18F]mFBG can detect SNS dysfunction and predict HF before any signs of heart complications. Canadian Journal of Cardiology home. Opens in ...