title: Chemistry and biology of radiotracers that target changes in sympathetic and parasympathetic nervous systems in heart disease.
abstract: Following the discovery of the sympathetic and parasympathetic nervous system, numerous adrenoceptor drugs were radiolabeled and potent radioligands were prepared in order to image the β-adrenergic and the muscarinic systems. But the greatest effort has been in preparing noradrenaline analogs, such as norepinephrine, (11)C-metahydroxyephedrine, and (123)I-metaiodobenzylguanidine that measure cardiac sympathetic nerve varicosities. Given the technical and clinical challenges in designing and validating targeted adrenoceptor-binding radiotracers, namely the heavily weighted flow dependence and relatively low target-to-background ratio, both requiring complicated mathematic analysis, and the inability of targeted adrenoceptor radioligands to have an impact on clinical care of heart disease, the emphasis has been on radioligands monitoring the norepinephrine pathway. The chemistry and biology of such radiotracers, and the clinical and prognostic impact of these innervation imaging studies in patients with heart disease, are examined.
authors.affiliation: Molecular Tracer LLC, Bethesda, Maryland; and wceckelman@gmail.com.
authors.forename: William C
authors.initials: WC
authors.lastname: Eckelman
authors.affiliation: Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Vasken
authors.initials: V
authors.lastname: Dilsizian
mesh_terms: D019797:3-Iodobenzylguanidine; D004809:Ephedrine / Q000031:analogs & derivatives; D006321:Heart / Q000000981:diagnostic imaging* / Q000294:innervation*; D006331:Heart Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology; D006333:Heart Failure; D006801:Humans; D008024:Ligands; D009638:Norepinephrine / Q000737:chemistry; D010275:Parasympathetic Nervous System / Q000000981:diagnostic imaging* / Q000503:physiopathology; D011485:Protein Binding; D011877:Radionuclide Imaging; D013564:Sympathetic Nervous System / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D008024:Ligands; C065363:3-hydroxyephedrine; D019797:3-Iodobenzylguanidine; D004809:Ephedrine; D009638:Norepinephrine
keywords: cardiac innervation; fluoro-m-hydroxyphenethylguanidine; heart failure; hydroxyephedrine; metaiodobenzylguanidine; norepinephrine