OBJECTIVE Nicotine promotes smoking partly by binding to beta2-containing nicotinic acetylcholine receptors (beta2*-nAChRs) in the brain. Smoking one tobacco cigarette results in occupation of 80% of beta2*-nAChRs for more than 6 hours. This likely contributes to maintenance of smoking dependence and cessation difficulty. Developing nicotine vaccines could improve treatments. The authors used [123I]5-I-A-85380 single photon emission computed tomography (SPECT) to evaluate the effect of 3'-AmNic-rEPA on the amount of nicotine that binds to beta2*-nAChRs in smokers' brain cortical and subcortical regions. METHOD Eleven smokers who smoked an average of 19 cigarettes per day, had smoked for 10 years on average, and met criteria for nicotine dependence were given SPECT scans on two days: before and after immunization with 4-400 μg of 3'-AmNic-rEPA. On scan days, three 30-minute baseline emission scans were followed by intravenous administration of nicotine (1.5 mg/70 kg body weight) and up to nine 30-minute emission scans. RESULTS beta2*-nAChR availability was quantified as VT/fP (total distribution volume divided by free plasma concentration), and nicotine binding was derived by the Lassen plot approach. Immunization led to a 12.5% reduction in nicotine binding. Nicotine bound to beta2*-nAChRs correlated positively with nicotine injected before but not after vaccination. The daily number of cigarettes and desire for a cigarette decreased after vaccination. CONCLUSIONS This proof-of-concept study demonstrates that immunization with nicotine vaccine can reduce the amount of nicotine binding to beta2*-nAChRs and disrupt the relationship between administered nicotine and nicotine available to occupy beta2*-nAChRs.
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