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

Abstract PipISB [N‐(4‐fluoro‐benzyl)‐4‐(3‐(piperidin‐1‐yl)‐indole‐1‐sulfonyl)benzamide, 9] was identified as a selective high potency CB1 receptor ligand. Here we describe the labeling of 9 with positron‐emitters to provide candidate radioligands for imaging brain CB1 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, [11C]9 was prepared in one step from [11C]carbon monoxide, itself prepared from cyclotron‐produced [11C]carbon dioxide. In method B, [18F]9 was prepared from cyclotron‐produced [18F]fluoride ion in a two‐stage, four‐step synthesis with [18F]4‐fluoro‐benzyl bromide as a labeling agent. The radiosynthesis time for method A was 44 min; decay‐corrected radiochemical yields (RCYs) from [11C]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 [18F]fluoride ion ranged from 1.5 to 5.6% and specific radioactivities ranged from 200 to 348 GBq/µmol. With these methods, [11C]9 and [18F]9 may be prepared in adequate activity and quality for future evaluation as PET radioligands. Copyright © 2008 John Wiley & Sons, Ltd.