title: [High non-specific binding of the beta(1) -selective radioligand 2-(125)I-ICI-H].
abstract: OBJECTIVE
  As results of cardiac biopsies suggest, myocardial beta(1) -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac beta(2)-adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the opportunity to assess beta-adrenoceptors non-invasively. Among the novel racemic analogues of the established beta(1)-selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to beta(1)-adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective beta(1)-adrenergic radioligand in cardiac imaging.
  
  
  METHODS
  Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac beta-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-(125)I-ICI-H from the silylated precursor 2-SiMe(3)-ICI-H was established. The specific activity was 80 GBq/ micro mol, the radiochemical yield ranged from 70 to 80%.
  
  
  RESULTS
  The unlabelled compound 2-I-ICI-H showed high beta(1)-selectivity and -affinity in the in vitro competition studies. In vivo biodistribution studies apparently showed low affinity to cardiac beta-adrenoceptors. The radiolabelled counterpart 2-(125)I-ICI-H showed a high degree of non-specific binding in vitro and no specific binding to cardiac beta(1)-adrenoceptors in vivo.
  
  
  CONCLUSIONS
  Because of its high non-specific binding 2-(125)I-ICI-H is no suitable radiotracer for imaging in vivo.
authors.affiliation: Department of Nuclear Medicine, Münster University, Germany. riemanb@uni-muenster.de
authors.forename: B
authors.initials: B
authors.lastname: Riemann
authors.forename: M P
authors.initials: MP
authors.lastname: Law
authors.forename: K
authors.initials: K
authors.lastname: Kopka
authors.forename: St
authors.initials: S
authors.lastname: Wagner
authors.forename: S
authors.initials: S
authors.lastname: Luthra
authors.forename: V W
authors.initials: VW
authors.lastname: Pike
authors.forename: J
authors.initials: J
authors.lastname: Neumann
authors.forename: U
authors.initials: U
authors.lastname: Kirchhefer
authors.forename: W
authors.initials: W
authors.lastname: Schmitz
authors.forename: O
authors.initials: O
authors.lastname: Schober
authors.forename: M
authors.initials: M
authors.lastname: Schäfers
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001667:Binding, Competitive; D001713:Biphenyl Compounds / Q000493:pharmacokinetics*; D006321:Heart / Q000502:physiology; D051379:Mice; D008811:Mice, Inbred DBA; D011412:Propanolamines / Q000493:pharmacokinetics*; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014055:Tomography, Emission-Computed; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods*
chemical_list: C481040:2-I-ICI-H; D000319:Adrenergic beta-Antagonists; D001713:Biphenyl Compounds; D011412:Propanolamines; D019275:Radiopharmaceuticals; D018342:Receptors, Adrenergic, beta-1; C025716:ICI 89406; C033394:CGP 12177