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SummaryTo date, some non-selective b-adrenoceptor (b-AR) positron emission tomography (PET) radioligands are in clinical use, but no PET radioligand for the selective imaging of cardiac b 1 -ARs is clinically available. Therefore, the aim of this study was to develop a potential high-affinity PET radioligand for the b 1 -subtype of ARs. Here, the synthesis and in vitro evaluation of (S)-and, derivatives of the well-characterized b 1 -AR selective antagonist, ICI 89,406, are described. The (S)-isomer 8a shows both higher b 1 -AR selectivity and b 1 -AR affinity than the (R)-enantiomer 8b (selectivity: 40 800 vs 1580; affinity: K I1 ¼ 0:049 nM vs K I1 ¼ 0:297 nM). Therefore, the 18 F-labelled analogue 8e of compound 8a was synthesized. While the direct nucleophilic 18 F-fluorination of the tosylate precursor 8d produced 8e in low radiochemical yields (42.9% decay-corrected) and specific activities (43.5 GBq/mmol at the end of synthesis (EOS), n ¼ 9) the alternative two-step synthesis of 8e from ethylene glycol di-p-tosylate 9, [ 18 F]fluoride ion and phenol precursor 8f gave satisfying results (16.4 AE 3.2% radiochemical yield (decay-corrected), 99.7 AE 0.5% radiochemical purity, 40 AE 8 GBq/mmol specific activity at the EOS within 174 AE 3 min from the end of bombardment (EOB) (n ¼ 5)).

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).

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