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

✍ Scribed by Takahiro Matsuya; Hiroyuki Takamatsu; Yoshihiro Murakami; Akihiro Noda; Kazuhiko Osoda; Rikiya Ichise; Yuji Awaga; Shintaro Nishimura

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 224 KB
• Volume: 48
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.958

✦ Synopsis

Abstract

We demonstrated the synthesis of carbon‐11 labeled 17‐α‐hydroxy‐11‐β‐/4‐/[methyl]‐[1‐methylethyl]‐aminophenyl/‐17__α__‐[prop‐1‐ynyl]esta‐4‐9‐diene‐3‐one (RU40555), a selective glucocorticoid receptor (GR) antagonist, and examined the in vivo profile of [^11^C]RU40555. [^11^C]RU40555 was synthesized by direct N‐methylation with [^11^C]CH~3~OTf at 60°C for 5 min and an injectable solution of [^11^C]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 [^11^C]RU40555 were examined. ADX significantly decreased plasma corticosterone levels, and significantly increased brain accumulation of [^11^C]RU40555. We succeeded in developing a rapid automated synthesis method for [^11^C]RU40555, a GR antagonist, and showed [^11^C]RU40555 had a potential as a PET tracer for mapping GR. Copyright © 2005 John Wiley & Sons, Ltd.