(S)-(-)-[11C]nicotine binding assessed by PET: a dual tracer model evaluated in the rhesus monkey brain.
A dual tracer model, consisting of the administration of 15O-water and (S)-(-)-[11C]nicotine in close succession, is suggested to assess nicotine binding in the brain. Regional cerebral blood flow (rCBF) determined by 15O-water was used to flow compensate two nicotine model parameters, k1 and k2, obtained in a two-compartment kinetic model. In the present study, this dual tracer approach was evaluated in the rhesus monkey by altering the rCBF or by administering (S)-(-)-[11C]nicotine at either high or low specific radioactivity. The model parameter, k2' = k2/rCBF, was found to be independent of rCBF in different regions of interest in the monkey brain. The parameter, k2', increased significantly when (S)-(-)-[11C]nicotine was given at low specific radioactivity, indicating lower nicotine binding in the brain. Thus, this observation implies an influence on specific receptor binding on the corrected efflux rate constant. This dual tracer model may be useful in evaluating nicotine binding changes in the human brain and the effect of drug treatment in neurodegenerative disorders such as Alzheimer disease.
Department of Biomedical Radiation Sciences, Subfemtomole Biorecognition Project, Uppsala University, Sweden.
H
H
Lundqvist
A
A
Nordberg
P
P
Hartvig
B
B
Långström
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D009538:Nicotine / Q000493:pharmacokinetics*; D010104:Oxygen Radioisotopes / Q000493:pharmacokinetics; D011978:Receptors, Nicotinic / Q000378:metabolism; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D010104:Oxygen Radioisotopes; D011978:Receptors, Nicotinic; D009538:Nicotine