[11C]RN5: a new agent for the in vivo imaging of myocardial receptors

The radiolabelling with the positron-emitter Carbon-11 and the biological evaluation in rats of3-[2-[4-(2-[11C]methoxyphenyl)piperazin-1-yl]ethyl] pyrimido[5,4-b]indole-2,4-dione([11C]RN5), a1-adrenoceptor antagonist (Ki= 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°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/mmol. 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.