[11C]RN5: A new agent for the in vivo imaging of myocardial α1-adrenoceptors

The radiolabelling with the positron-emitter Carbon-11 and the biological evaluation in rats of 3-[2-[4-(2-[C-11]methoxyphenyl)piperazin-1 -yl]ethyl] pyrimido [5,4-b] indole-2,4-dione ([C-11]RN5), alpha(1)-adrenoceptor antagonist (K-i = 0.21 nM), as a putative radioligand for the noninvasive assessment of alpha(1)-adrenoceptors with positron emission tomography (PET) is reported. The radiosynthesis procedure consisted of O-methylation of des-methyl precursor with [C-11]methyl iodide in the presence of potassium hydroxide in dimethylformamide (DMF) at 80 degreesC. [C-11]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/mumol. Pre-clinical studies in rats showed a high uptake of [C-11]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 [C-11]RN5 is due to specific binding to alpha(1)-adrenoceptors. Our results indicate that [C-11]RN5 is suitable to be further developed as a potential radioligand for the in vivo PET imaging of myocardial alpha(1)-adrenoceptors in humans. (C) 2002 Published by Elsevier Science B.V