Medical Physics Seminar – Monday, October 7, 2013
Imaging the α4β2 Nicotinic Acetylcholine Receptor System with PET
Ansel Hillmer (student of Dr. Bradley Christian)
Research Assistant, Department of Medical Physics, UW-School of Medicine & Public Health, Madison, WI - USA -
The nicotinic acetylcholine receptor (nAChR) system plays a major role in the pathology related to substance addiction and abuse, Alzheimer’s Disease, neuropsychiatric illnesses and lung cancer, among other illnesses. The positron emission tomography (PET) radioligand [18F]nifene was developed to target the α4β2 subtype of nAChRs. This work presents a full characterization of the [18F]nifene kinetic profile via compartment modeling in preclinical experiments. These studies include measurements of receptor density (Bmax) and in vivo radioligand-receptor affinity (1/KDapp), which more completely convey the underlying physiology of [18F]nifene binding than standard binding potential metrics. The favorable kinetics of [18F]nifene were exploited in experiments designed to detect altered synaptic acetylcholine concentrations induced by acetylcholinesterase inhibitors, drugs thought to ameliorate the cognitive effects of Alzheimer’s Disease. These findings provide strong support for the development and translation of [18F]nifene into human studies to clinically study the nAChR system.