Gender Differences in Binding Kinetics of Nicotinic Acetylcholine Receptors Using microPET/CT with 2-[18F]FA-85380

Conclusions: The brain regional distribution of nAChR binding by 2-[18F]-A85380, specifically highest uptake within thalamus in contrast to the weakest binding within the cerebellum, is consistent with findings from human studies. The elevated maximum binding of 2-[18F]FA-85380 in females may suggest a higher density of nAChR in the female brain. In addition, one of the hypotheses of the nicotine binding mechanisms is that the ligand/receptor complex is trapped in the intracellular acidic vesicles. The slower dissociation rate observed in females may be indicative of stronger trapping. Together, these observed gender differences in mice may reflect gender differences in the response to nicotine exposure as well as to nicotine cessation treatments in humans. Therefore, more investigation into the binding kinetics of 2-[18F]FA-85380 and other nAChR ligands is necessary. The differences in kinetics and displaceable binding should provide insight into the cellular mechanism of nicotine induced nAChR upregulation and how nicotine agonists alter this process.

Source: Journal of Nuclear Medicine - May 14, 2020 Category: Nuclear Medicine Authors: Mitchell, S., Zhang, H., Bhuiyan, M., Tsai, H.-M., Leoni, L., Freifelder, R., Roman, B., Kao, C.-M., Zhuang, X., Green, W., Mukherjee, J., Chen, C.-T. Tags: Basic Science - Synaptic activity and other mechanisms Source Type: research