Radiolabeling of a high potency cannabinoid subtype-1 receptor ligand, N-(4-fluoro-benzyl)-4-(3-(piperidin-1-yl)-indole-1-sulfonyl)benzamide (PipISB), with carbon-11 or fluorine-18
✍ Scribed by Sean R. Donohue; Christer Halldin; Magnus Schou; Jinsoo Hong; Lee Phebus; Eyassu Chernet; Stephen A. Hitchcock; Kevin M. Gardinier; Kevin M. Ruley; Joseph H. Krushinski; John Schaus; Victor W. Pike
- Publisher
- John Wiley and Sons
- Year
- 2008
- Tongue
- French
- Weight
- 216 KB
- Volume
- 51
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
PipISB [N‐(4‐fluoro‐benzyl)‐4‐(3‐(piperidin‐1‐yl)‐indole‐1‐sulfonyl)benzamide, 9] was identified as a selective high potency CB~1~ receptor ligand. Here we describe the labeling of 9 with positron‐emitters to provide candidate radioligands for imaging brain CB~1~ receptors with positron emission tomography (PET). The radiolabeling of 9 was achieved by two methods, method A with carbon‐11 and method B with fluorine‐18. In method A, [^11^C]9 was prepared in one step from [^11^C]carbon monoxide, itself prepared from cyclotron‐produced [^11^C]carbon dioxide. In method B, [^18^F]9 was prepared from cyclotron‐produced [^18^F]fluoride ion in a two‐stage, four‐step synthesis with [^18^F]4‐fluoro‐benzyl bromide as a labeling agent. The radiosynthesis time for method A was 44 min; decay‐corrected radiochemical yields (RCYs) from [^11^C]carbon monoxide ranged from 3.1 to 11.6% and specific radioactivities ranged from 21 to 67 GBq/µmol. The radiosynthesis time for method B was 115 min; RCYs from [^18^F]fluoride ion ranged from 1.5 to 5.6% and specific radioactivities ranged from 200 to 348 GBq/µmol. With these methods, [^11^C]9 and [^18^F]9 may be prepared in adequate activity and quality for future evaluation as PET radioligands. Copyright © 2008 John Wiley & Sons, Ltd.