[11C]RN5: a new agent for the in vivo imaging of myocardial alpha1-adrenoceptors.
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.
Matarrese
Mario
M
Institute of Molecular Bioimaging and Physiology-CNR, University of Milano/Bicocca, Institute San Raffaele, Via Olgettina 60, 20132, Milan, Italy.
Moresco
Rosa M
RM
Romeo
Giuseppe
G
Turolla
Elia A
EA
Simonelli
Pasquale
P
Todde
Sergio
S
Belloli
Sara
S
Carpinelli
Assunta
A
Magni
Fulvio
F
Russo
Filippo
F
Galli Kienle
Marzia
M
Fazio
Ferruccio
F
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
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