Hohe unspezifische Bindung des β1-selektiven Radioliganden 2-125I-ICI-H

Aim: As results of cardiac biopsies suggest, myocardial β1 -adrenoceptor density is reduced in patients with chronic heart failure. However, changes in cardiac β2 -adrenoceptors vary. With suitable radiopharmaceuticals single photon emission computed tomography (SPECT) and positron emission tomography (PET) offer the op-portunity to assess β -adrenoceptors non-invasively. Among the novel racemic analogues of the established β 1 -selective adrenoceptor antagonist ICI 89.406 the iodinated 2-I-ICI-H showed high affinity and selectivity to β 1 -adrenoceptors in murine ventricular membranes. The aim of this study was its evaluation as a putative sub-type selective β1 -adrenergic radioligand in cardiac imag-ing. Methods: Competition studies in vitro and in vivo were used to investigate the kinetics of 2-I-ICI-H binding to cardiac β-adrenoceptors in mice and rats. In addition, the radiosynthesis of 2-125 I-ICI-H from the silylated precursor 2-SiMe3-ICI-H was established. The specific activity was 80 GBq/µmol, the radiochemical yield ranged from 70 to 80%. Results: The unlabelled compound 2-I-ICI-H showed high β1 -selectivity and -affinity in the in vitro competi-tion studies. In vivo biodistribution studies apparently showed low affinity to cardiac β -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 β1 -adrenoceptors in vivo. Conclusion: Because of its high non-specific binding 2-125 I-ICI-H is no suitable radiotracer for imaging in vivo.