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

10 Participants Needed

Trial Summary

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 data supports the effectiveness of the drug 18F-mFBG for cardiovascular disease?

Research on a similar drug, 123I-mIBG, shows it can help predict heart problems in patients with heart failure. A study also suggests that an F-18-labeled version, like 18F-mFBG, might be useful for identifying heart issues in a rat model, indicating potential effectiveness in humans. ^{1 2 3 4 5}

How does the drug 18F-mFBG differ from other treatments 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 heart conditions. This makes it potentially more effective in identifying ischemic and viable heart tissue, which can improve diagnosis and treatment planning for cardiovascular diseases. ^{4 6 7 8 9}

What is the purpose of this trial?

This is a Phase 1/2 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for quantification of myocardial sympathetic innervation.

Research Team

Vikram Agarwal, MD

Principal Investigator

Mount Sinai Morningside

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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]

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]

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]

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]

References

1. Germany 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. [2022]

2. United States 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). [2022]

3. Italy 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. [2016]

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

Feasibility of myocardial PET imaging using a benzylguanidine analog: meta-(3-[18F]fluoropropyl)benzylguanidine ([18F]mFPBG). [2019]

5. Japan 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. [2016]

6. Japan 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. [2018]

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

Uptake and retention kinetics of para-fluorine-18-fluorobenzylguanidine in isolated rat heart. [2016]

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

Cardiac sympathetic imaging with mIBG in heart failure. [2016]

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

Non-18F-FDG/18F-NaF Radiotracers Proposed for the Diagnosis and Management of Diseases of the Heart and Vasculature. [2021]