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

• Published in: Journal of labelled compounds & radiopharmaceuticals 2005-08, Vol.48 (9), p.657-668
• Main Authors: Matsuya, Takahiro, Takamatsu, Hiroyuki, Murakami, Yoshihiro, Noda, Akihiro, Osoda, Kazuhiko, Ichise, Rikiya, Awaga, Yuji, Nishimura, Shintaro
• Format: Article
• Language: English
• Subjects: [11C]RU40555; Biological and medical sciences; Contrast media. Radiopharmaceuticals; glucocorticoid receptor antagonist; Medical sciences; PET; Pharmacology. Drug treatments
• ISSN: 0362-4803; 1099-1344
• DOI: 10.1002/jlcr.958

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.