The development of receptor-binding radiotracers has evolved from a goal of high affinity compounds to give high target to non target ratios to compounds of slightly lesser affinity so that they can reach either steady state after bolus injection or equilibrium after infusion. The other important advance is the ability to measure endogenous neurotransmitter, using various lower affinity muscarinic acetylcholine receptor radioligands. There have been a number of clinical studies that elucidated the mechanism of action of new pharmaceuticals in vivo using external imaging. These include studies of drug interaction of olanzapine, risperidone, clozapine, donepezil, and phenserine with the muscarinic receptor. There have been fewer studies monitoring the effect of therapy in Alzheimers disease, but those pilot studies give great hope that monitoring therapy is a real possibility. Radioligands for the muscarinic receptor, for ACh esterase, and to measure the concentration of acetylcholine have now been developed, A number of studies in small populations have identified changes in mild to moderate Alzheimers disease and, perhaps more importantly, changes in radioligand binding have been identified in clinically normal subjects genetically predisposed to Alzheimers disease by virtue of the epsilon 4+ variant of the APOE gene. Large scale clinical studies are now needed to delineate the true value of these radiotracers in clinical situations. PET and SPECT imaging hold the promise of monitoring the effect of pharmaceuticals in a wide variety of diseases using non-invasive external imaging of the muscarinic cholinergic system.
Keywords: Muscarinic receptor, acetylcholine, Knock-Out mice, HPLC-MS, IQNB, FP-TZTP
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