Synthesis and in vivo evaluation of [11C]ICI 118551 as a putative subtype selective beta2-adrenergic radioligand

Erytro-(+/-)-1-[2,3-(dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[ iso-propylamino]-2-butanol (ICI 118551) a potent clinically used beta2 adrenergic antagonist, was labelled with carbon-11 (t1/2 = 20.4 min) as a potential radioligand for the non-invasive assessment of beta2 adrenergic receptors in the lung with positron emission tomography (PET). The radiolabelled compound was prepared by reductive N-alkylation of its des-isopropyl precursor with [2-11C]acetone. (+/-)-[11C]ICI 118551 was obtained in greater than 98% radiochemical purity in 30 min with a radiochemical yield of 15 + 5% (non-decay corrected) and a specific radioactivity 2.5 +/- 0.5 Ci/micromol. The biological evaluation of racemic erythro (+/-)-[11C]ICI 118551 in rats and Macaca Nemestrina shows a high radioactivity uptake in lung and heart. However, in both animal models no detectable displacement of lung radioactivity concentration was observed after pre-treatment with propranolol or ICI 118551, which indicates that in this organ, radioligand uptake is mostly due to non-specific binding. The biological data suggest that erythro (+/-)-[11C]ICI 118551 is not adequate to be further developed as a tracer for beta2 adrenergic receptor imaging in vivo.