title: Synthesis and in vivo evaluation of [11C]ICI 118551 as a putative subtype selective beta2-adrenergic radioligand.
abstract: 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.
authors.affiliation: INB-CNR, University of Milano-Bicocca, Institute H.S. Raffaele, Milan, Italy.
authors.forename: R M
authors.initials: RM
authors.lastname: Moresco
authors.forename: M
authors.initials: M
authors.lastname: Matarrese
authors.forename: D
authors.initials: D
authors.lastname: Soloviev
authors.forename: P
authors.initials: P
authors.lastname: Simonelli
authors.forename: M
authors.initials: M
authors.lastname: Rigamonti
authors.forename: C
authors.initials: C
authors.lastname: Gobbo
authors.forename: S
authors.initials: S
authors.lastname: Todde
authors.forename: A
authors.initials: A
authors.lastname: Carpinelli
authors.forename: M G
authors.initials: MG
authors.lastname: Kienle
authors.forename: F
authors.initials: F
authors.lastname: Fazio
mesh_terms: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000818:Animals; D002250:Carbon Radioisotopes / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D005260:Female; D008168:Lung / Q000378:metabolism*; D008254:Macaca nemestrina; D008297:Male; D011412:Propanolamines / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D002250:Carbon Radioisotopes; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; C026777:ICI 118551