Radiosynthesis of 2‐[6‐chloro‐2‐(4‐iodophenyl)imidazo[1,2‐<i>a</i>]pyridin‐3‐yl]‐<i>N</i>‐ethyl‐<i>N</i>‐[¹¹C]methyl‐acetamide, [¹¹C]CLINME, a novel radioligand for imaging the peripheral benzodiazepine receptors with PET

Abstract

Abstract Recently, a new 2‐(iodophenyl)imidazo[1,2‐ a ]pyridineacetamide series has been developed as iodine‐123‐labelled radioligands for imaging the peripheral benzodiazepine receptors using single photon emission tomography. Within this series, 2‐[6‐chloro‐2‐(4‐iodophenyl)‐imidazo[1,2‐ a ]pyridin‐3‐yl]‐ N ‐ethyl‐ N ‐methyl‐acetamide (CLINME) was considered as an appropriate candidate for positron emission tomography imaging and was isotopically labelled with carbon‐11 ( T 1/2 : 20.38 min) at the methylacetamide side chain from the corresponding nor ‐analogue using [ 11 C]methyl iodide and the following experimental conditions: (1) trapping at −10°C of [ 11 C]methyl iodide in a 1/2 (v:v) mixture of DMSO/DMF (300 µl) containing 0.7–1.0 mg of the precursor for labelling and 3–5 mg of powdered potassium hydroxide (excess); (2) heating the reaction mixture at 110°C for 3 min under a nitrogen stream; (3) diluting the residue with 0.6 ml of the HPLC mobile phase; and (4) purification using semi‐preparative HPLC (Zorbax ® SB18, Hewlett Packard, 250 × 9.4 mm). Typically, starting from a 1.5 Ci (55.5 GBq) [ 11 C]CO 2 production batch, 120−150 mCi (4.44–5.55 GBq) of [ 11 C]CLINME were obtained (16–23% decay‐corrected radiochemical yield, n =12) within a total synthesis time of 24–27 min (Sep‐pak ® Plus‐based formulation included). Specific radioactivities ranged from 0.9 to 2.7 Ci/µmol (33.3–99.9 GBq/µmol) at the end of radiosynthesis. Copyright © 2007 John Wiley &amp; Sons, Ltd.