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

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 (T1/2: 20.38 min) at the methylacetamide side chain from the corresponding nor-analogue using [11C]methyl iodide and the following experimental conditions: (1) trapping at −10°C of [11C]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) [11C]CO2 production batch, 120−150 mCi (4.44–5.55 GBq) of [11C]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 & Sons, Ltd.