Imaging muscarinic cholinergic receptors using I-123-paraiododexetimide and emission computed tomography

Dexetimide is a high affinity muscarinic cholinergic receptor (MR) antagonist which binds preferentially to MR in vivo. The corresponding optical isomer of dexetimide is levetimide (LEV) which binds to MR with a thousand-fold lower affinity. Paraiododexetimide (IDEX) has an affinity slightly less than dexetimide (KD = 2.7 nM). Following the administration of I-125 IDEX (10 μg/kg,IV) to mice high radioactivity concentrations in the striatum and cerebral cortex and a low radioactivity concentration in the cerebellum were observed; this distribution corresponds to the known distribution of MR in the brain. Following the injection of I-125-ILEV a low and uniform radioactivity concentration was observed throughout the brain. Preliminary imaging studies using an Anger camera and I-123-IDEX in a baboon showed high radioactivity in the brain and parotid gland. The radioactivity in the parotid gland diminished with time whereas the radioactivity in the brain increased over the 90 min. imaging period, which suggests high affinity binding to MR in the brain. These results demonstrate the feasibility of imaging MR using single photon emission computed tomography and I-123-IDEX