Open-Label Study of 18F-mFBG for Imaging Myocardial Sympathetic Innervation

This is a Phase 1/2 study evaluating the positron-emitting radiopharmaceutical 18F-mFBG as an imaging agent for quantification of myocardial sympathetic innervation. The first part of the study will examine control subjects, patients with very low likelihood of coronary heart disease. This initial part will determine optimal imaging procedures for studying uptake and clearance of 18F-mFBG in myocardial sympathetic neurons and provide preliminary data for estimating radiation dosimetry in adults and developing reference files for quantification of normal and abnormal levels of the radiopharmaceutical. The second part will examine a group of stable patients with New York Heart Association (NYHA) class 2 heart failure (HF) and reduced left ventricular (LV) systolic function (LV ejection fraction (EF) ≤35%). The primary objectives of the second part will be to:

• document the degree to which 18F-mFBG uptake in the heart is reduced and
• characterize the distribution of regional abnormalities in relation to findings on other cardiac imaging studies such as myocardial perfusion (MP) and magnetic resonance (MR) imaging.

Effectiveness of 18F-mFBG will be judged in relation to historical experience with other nuclear imaging agents for cardiac sympathetic innervation imaging such as a 123I-meta-iodobenzylguanidine (mIBG) and 11C-hydroxyephedrine (HED).

Inclusion criteria

• ≥ 18 years of age at study entry
• 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.

For control subjects:

• Subject is either:

• <40 years old and has a likelihood assessment for CAD <10%, or
• 40-50 years old, has a likelihood assessment for CAD <10%, and a normal stress MPI study or stress echocardiography performed within 6 months before study entry, or
• Without significant coronary atherosclerotic disease (no arterial stenosis with >30% narrowing) as demonstrated by a coronary angiography performed with 6 months before study entry.

For heart failure subjects:

• Diagnosed with HF at least 1 year before enrollment.
• HF classification NYHA Class II at enrollment.
• Rest left ventricular ejection fraction (LVEF) ≤35% measured by an appropriate method (e.g., radionuclide or contrast ventriculography, ECG-gated SPECT MPI, or echocardiography) within 180 days prior to the study imaging procedure, with no change in clinical condition since the LVEF measurement.
• Primary prevention ICD, implanted at least 6 months before enrollment.
• Clinically stable for at least 30 days before enrollment (e.g., not experiencing continuing chest pain, hemodynamic instability, or clinically significant arrhythmia (including ICD discharge)) and remains stable to the time of the study imaging procedure.

Exclusion criteria

• Previously entered into this study or has participated in any other investigational medicinal product or medical device study within 30 days of enrollment.
• History or suspicion of significant allergic reaction or anaphylaxis to any components of the 18F-mFBG imaging agent.
• 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.
• Presents with any other clinically active, serious, life-threatening disease with a life expectancy of less than 1 year or where participation in the study might compromise the management of the subject or other reason that in the judgment of the investigator(s) makes the subject unsuitable for participation in the study.
• Serious non-cardiac medical condition associated with significant elevation of plasma catecholamines including pheochromocytoma.
• Claustrophobic or has a movement disorder that prevents him/her from lying still in a supine position for up to an hour at a time.
• Renal insufficiency (serum creatinine >3.0 mg/dL).
• Use of medications that are known to interfere with uptake of NET-dependent agents and these medications cannot be safely withheld 24 hours before study procedures.
• Participated in a research study using ionizing radiation in the previous 12 months.
• For control subjects: a history of Type I or Type II Diabetes Mellitus, signs/symptoms of neurological disease (e.g., Parkinson's Disease, Multiple System Atrophy, Parkinsonian syndromes), or other diseases known to affect the sympathetic nervous system.