Synthesis and in vivo evaluation of [C-11]ICI 118551 as a putative subtypeselective beta(2)-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 beta(2) adrenergic antago nist, was labelled with carbon-11 (t(1/2) = 20.4 min) as a potential radiol igand for the non-invasive assessment of beta(2) adrenergic receptors in th e lung with positron emission tomography (PET). The radiolabelled compound was prepared by reductive N-alkylation of its des-isopropyl precursor with [2-C-11]acetone. (+/-)-[C-11]ICI 118551 was obtained in greater than 98% ra diochemical purity in 30 min with a radiochemical yield of 15 +/- 5% (non-d ecay corrected) and a specific radioactivity 2.5 +/- 0.5 Ci/mu mol. The bio logical evaluation of racemic erythro (+/-)-[C-11]ICI 118551 in rats and Ma cara Nemestrina shows a high radioactivity uptake in lung and heart. Howeve r, in both animal models no detectable displacement of lung radioactivity c oncentration was observed after pre-treatment with propranolol or ICI 11855 1, which indicates that in this organ, radioligand uptake is mostly due to non-specific binding. The biological data suggest that erythro (+/-)-[C-11] ICI 118551 is not adequate to be further developed as a tracer for beta(2) adrenergic receptor imaging in vivo. (C) 2000 Elsevier Science B.V. All rig hts reserved.