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

Abstract

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.