title: [11C]RN5: a new agent for the in vivo imaging of myocardial alpha1-adrenoceptors.
abstract: The radiolabelling with the positron-emitter Carbon-11 and the biological evaluation in rats of 3-[2-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]ethyl]pyrimido[5,4-b]indole-2,4-dione ([11C]RN5), alpha1-adrenoceptor antagonist (K(i)=0.21 nM), as a putative radioligand for the non-invasive assessment of alpha1-adrenoceptors with positron emission tomography (PET) is reported. The radiosynthesis procedure consisted of O-methylation of des-methyl precursor with [11C]methyl iodide in the presence of potassium hydroxide in dimethylformamide (DMF) at 80 degrees C. [11C]RN5 was obtained in >99% radiochemical purity in 25 min with a radiochemical yield in the 20-30% range, end of synthesis (EOS) (non-decay corrected) and a specific radioactivity of 92.5+/-18.5 GBq/micromol. Pre-clinical studies in rats showed a high uptake of [11C]RN5 in heart, spleen, adrenal gland, lung and kidney but not in the brain. Inhibition studies with high doses of different adrenergic antagonists indicate that more than 70% of myocardial uptake of [11C]RN5 is due to specific binding to alpha1-adrenoceptors. Our results indicate that [11C]RN5 is suitable to be further developed as a potential radioligand for the in vivo PET imaging of myocardial alpha1-adrenoceptors in humans.
authors.affiliation: Institute of Molecular Bioimaging and Physiology-CNR, University of Milano/Bicocca, Institute San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Matarrese
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Moresco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Romeo
authors.forename: Elia A
authors.initials: EA
authors.lastname: Turolla
authors.forename: Pasquale
authors.initials: P
authors.lastname: Simonelli
authors.forename: Sergio
authors.initials: S
authors.lastname: Todde
authors.forename: Sara
authors.initials: S
authors.lastname: Belloli
authors.forename: Assunta
authors.initials: A
authors.lastname: Carpinelli
authors.forename: Fulvio
authors.initials: F
authors.lastname: Magni
authors.forename: Filippo
authors.initials: F
authors.lastname: Russo
authors.forename: Marzia
authors.initials: M
authors.lastname: Galli Kienle
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Fazio
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000493:pharmacokinetics*; D000818:Animals; D001665:Binding Sites; D002250:Carbon Radioisotopes; D007211:Indoles / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008024:Ligands; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011743:Pyrimidines / Q000493:pharmacokinetics*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: C475198:3-(2-(4-(2-(11C)methoxyphenyl)piperazin-1-yl)ethyl)pyrimido(5,4-b)indole-2,4-dione; D000317:Adrenergic alpha-Antagonists; D002250:Carbon Radioisotopes; D007211:Indoles; D008024:Ligands; D011743:Pyrimidines; D019275:Radiopharmaceuticals; D018340:Receptors, Adrenergic, alpha-1