RT Journal Article
SR Electronic
T1 Effect of anti-nicotine immunization with NIC-002 vaccine on brain nicotine accumulation during cigarette smoking.
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 30
OP 30
VO 54
IS supplement 2
A1 Mukhin, Alexey
A1 Garg, Sudha
A1 Zuo, Yantao
A1 Nazih, Rachid
A1 Behm, Frederique
A1 Bottoli, Ivan
A1 Rose, Jed
A1 Garg, Pradeep
YR 2013
UL http://jnm.snmjournals.org/content/54/supplement_2/30.abstract
AB 30 Objectives Anti-nicotine immunization could have utility in aiding smoking cessation. This study assessed the effect of anti-nicotine immunization on brain nicotine accumulation during cigarette smoking using PET. Methods 29 regular smokers (≥10 cigarettes/day) received 4 vaccinations each with 100 μg NIC002 in Alum, (Novartis Pharma AG). The first PET session was performed before the first vaccination and the second at two weeks after the last vaccination. The subject’s head was scanned over 6 min (245 frames) after inhalation of a single puff of smoke from a cigarette containing 11C-(S)-nicotine. The vaccination-induced serum anti-body binding capacity (bound/free nicotine ratio, B/F) was assessed using 3H-(S)-nicotine and ultrafiltration. Results The vaccine was safe and well tolerated. Vaccination resulted in a statistically significant but highly variable increase (CV=88%) in serum binding capacity B/F = 0.18 ± 0.03 (mean ± SE, n=29, p<.001). In 10 participants with the highest B/F values vaccination produced a small but significant (p<.05) reduction in brain nicotine Cmax and AUC (0-6min) values by 15±6% and 15±7%, respectively. In the 10 participants with intermediate B/F values vaccination produced increases (p<.03) in Cmax and AUC values by 18±7% and 18±7%, respectively. In the group with the lowest B/F values (n=9) no changes in Cmaxand AUC were observed (1±8% and 2±7%, respectively). The Kd values for binding nicotine with post vaccination serum were almost two times higher in the group with intermediate vs. the group with the highest B/F values (600±140 nM vs. 310±50 nM, p<.05). The respective Bmax values were 170±30 nM and 130±20 nM. Conclusions Anti-nicotine immunization can produce both a decrease and an increase in brain nicotine accumulation during smoking, dependent on the quality (affinity) and quantity of the produced antibodies. Research Support National Institute on Drug Abuse (Grant RC2DA028948 to Dr. Mukhin) and Novartis Pharma AG.