In vitro and in vivo characterization of 4-[¹²⁵I]iododexetimide binding to muscarinic cholinergic receptors in the rat heart

4-[¹²⁵I]iododexetimide binding to muscarinic cholinergic receptors (mAChR) was evaluated in the rat heart. 4-[¹²⁵I]iododexetimide displayed high in vitro affinity (Kd = 14.0 nM) for rat myocardial mAChR. In vivo, there was high accumulation of 4-[¹²⁵I]iododexetimide in the rat atrium and ventricle which could be blocked by ~60% by preinjection of atropine. In contrast, accumulation of the radiolabeled stereoisomer, 4-[¹²⁵I]iodolevetimide, was 63% lower than 4-[¹²⁵I]iododexetimide and was not blocked by atropine. The blood clearance of 4-[¹²⁵I]iododexetimide was rapid, providing heart-to-blood ratios of up to 14:1; however, heart-to-lung and heart-to-liver ratios were below unity. The data indicate that 4-[¹²⁵I]iododexetimide binds potently to rat mAChR. However, since nonspecific binding is relatively high, it is not clear whether iododexetimide labeled with ¹²³I will be useful in SPECT imaging studies of myocardial mAChR. Further studies in humans are indicated.