title: Imaging cardiac SCN5A using the novel F-18 radiotracer radiocaine.
abstract: The key function of the heart, a well-orchestrated series of contractions, is controlled by cardiac action potentials. These action potentials are initiated and propagated by a single isoform of voltage gated sodium channels - SCN5A. However, linking changes in SCN5A expression levels to human disease in vivo has not yet been possible. Radiocaine, an F-18 radiotracer for positron emission tomography (PET), is the first SCN5A imaging agent in the heart. Explants from healthy and failing human hearts were compared using radiocaine autoradiography to determine that the failing heart has ~30% lower SCN5A levels - the first evidence of changes in SCN5A expression in humans as a function of disease. Paving the way for translational imaging, radiocaine proved to exhibit high in vivo specific binding to the myocardium of non-human primates. We envision that SCN5A measurements using PET imaging may serve as a novel diagnostic tool to stratify arrhythmia risk and assess for progression of heart failure in patients with a broad spectrum of cardiovascular diseases.
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, 149 13th Street, 02129 Charlestown, MA, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Hooker
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, 149 13th Street, 02129 Charlestown, MA, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Strebl
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, 149 13th Street, 02129 Charlestown, MA, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schroeder
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, 149 13th Street, 02129 Charlestown, MA, USA.
authors.forename: Hsiao-Ying
authors.initials: HY
authors.lastname: Wey
authors.affiliation: Department of Medicine, Division of Cardiology and Consortium for Fibrosis Research and Translation, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Amrut V
authors.initials: AV
authors.lastname: Ambardekar
authors.affiliation: Department of Medicine, Division of Cardiology and Consortium for Fibrosis Research and Translation, University of Colorado - Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: McKinsey
authors.affiliation: Harvard Medical School, Massachusetts General Hospital, Martinos Center for Biomedical Imaging, 149 13th Street, 02129 Charlestown, MA, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schoenberger
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001345:Autoradiography; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006321:Heart / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006333:Heart Failure / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics* / Q000378:metabolism; D009924:Organ Culture Techniques; D010215:Papio; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005462:Fluorine Radioisotopes; D062554:NAV1.5 Voltage-Gated Sodium Channel; D019275:Radiopharmaceuticals; C568320:SCN5A protein, human; C000615276:Fluorine-18