Synthesis and evaluation of [11C]RU40555, a selective glucocorticoid receptor antagonist

We demonstrated the synthesis of carbon‐11 labeled 17‐α‐hydroxy‐11‐β‐/4‐/methyl]‐1‐methylethyl]‐aminophenyl/‐17α‐prop‐1‐ynyl]esta‐4‐9‐diene‐3‐one (RU40555), a selective glucocorticoid receptor (GR) antagonist, and examined the in vivo profile of ¹¹C]RU40555. ¹¹C]RU40555 was synthesized by direct N‐methylation with ¹¹C]CH₃OTf at 60°C for 5 min and an injectable solution of ¹¹C]RU40555 was obtained in 31 min at the end of bombardment. The decay‐corrected radiochemical yield was 19%, the specific radioactivity was 57.5±14.0 GBq/µmol, and the radiochemical purity was more than 99% as determined by HPLC. In rat experiments, the effects of adrenalectomy (ADX) on brain accumulation of ¹¹C]RU40555 were examined. ADX significantly decreased plasma corticosterone levels, and significantly increased brain accumulation of ¹¹C]RU40555. We succeeded in developing a rapid automated synthesis method for ¹¹C]RU40555, a GR antagonist, and showed ¹¹C]RU40555 had a potential as a PET tracer for mapping GR. Copyright © 2005 John Wiley & Sons, Ltd.