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

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 (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 x 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.