Interestingly, in the smokers at 1 day of abstinence, the levels of total parent of the radiotracer were significantly lower, but normalized quickly, by 1 week of abstinence. This highlights the impact of nicotine or another chemical in tobacco smoke on metabolism, e.g., because nicotine was still present, it may have changed the metabolism of the radiotracer, resulting in lower total parent at 1 day of abstinence. Cytochrome P450 (CYP 2A6) is primarily responsible for the metabolism of nicotine to its main metabolite cotinine53. There is evidence that nicotine is metabolized faster in smokers than in nonsmokers and there are genetically-mediated differences in the metabolism of nicotine in smokers54. Additionally, nicotine can interfere with metabolism of other drugs55. Consistently, we expect that [123I]5-IA is metabolized in the liver by enzymes in the cytochrome P450 family, such as CYP2A6, which acts on nicotine, and CYP2B6 and CYP2D6, which catalyze the dealkylation of aromatic ethers56, 57. In radiotracer imaging studies it is imperative that brain uptake is corrected for radiotracer metabolism, since differences in metabolism of the radiotracer determine how much radiotracer
