Preclinical evaluation of an 18F-labelled β1-adrenoceptor selective radioligand based on ICI 89,406

Abstract

Purpose-Radioligand binding studies indicate a down-regulation of myocardial β 1 -adrenoceptors (β 1 -AR) in cardiac disease which may or may not be associated with a decrease in β 2 -ARs. We have chosen ICI 89,406, a β 1 -selective AR antagonist, as the lead structure to develop new β 1 -AR radioligands for PET and have synthesised a fluoro-ethoxy derivative (F-ICI).

PET imaging of the autonomic myocardial function: methods and interpretation

“…However, this has not yet been visualized. Recent developments have led to the introduction of [ 18 F] labelled β 1 -adrenocepter antagonist ICI89406 ([ 18 F]-FICI); unfortunately, this PET compound proofed to be aspecific [ 18 ]. The frequency of β-blocker therapy in heart failure population limits the utility of adrenoceptor radioligands, as accurate quantitative imaging necessitates discontinuation of this therapy.…”

Synthesis and Cardiac Imaging of 18F-Ligands Selective for β1-Adrenoreceptors

“…In contrast, the β 1 -AR selective antagonist ICI 89,406 ( 1 ; Scheme ) has previously been shown to produce effective blockage of β 1 -AR during exercise in patients with angina pectoris . As such, Schaefer et al chose this compound as their lead structure in the development of new β 1 -AR selective ligands for PET and SPECT. − Notably, the authors developed an O -methyl derivative of 1 , labeled with carbon-11 ([ 11 C]OMe-ICI 89,406; [ 11 C] 2 ), that exhibited high affinity and selectivity for β 1 -AR in vitro. Unfortunately, in vivo studies did not demonstrate high specific binding to myocardial β 1 -AR; rapid metabolism and high nonspecific binding in the myocardium were observed …”