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See prior figure for comparable study in rats.
Background. We previously showed that miconazole, a topical antifungal agent, can inhibit defluorination of radiotracers that are metabolized in the liver by a particular P450 enzyme (CYP2E1). We could not use miconazole in humans because of its moderate toxicity when given orally at high doses. Instead, we used disulfiram (Antabuse®), which is taken by alcoholics to maintain sobriety. Disulfiram is one of the most potent inhibitors of CYP2E1. A single oral dose of disulfiram, which an alcoholic would take every day, markedly inhibited defluorination (i.e., reduced skull uptake of fluoride ion), increased brain uptake of the radioligand [18F]FCWAY, and more clearly showed binding to serotonin 5-HT1A receptors in man.
Legend. Horizontal [18F]FCWAY images before and after administration of disulfiram. Left) Baseline image at 2 h shows high activity in skull, consistent with the metabolism of [18F]FCWAY to [18F]fluoride ion. Right) A repeat PET scan in the same subject after disulfiram (500 mg on the prior night) shows a marked reduction of skull activity and better visualization of the brain.
Reference. Y.H. Ryu, J.-S. Liow, S.S. Zoghbi, M. Fujita, J. Collins, D. Tipre, J. Sangare, J. Hong, V.W. Pike, and R.B. Innis. Disulfiram inhibits defluorination of [18F]FCWAY, reduces bone radioactivity, and enhances visualization of radioligand binding to 5-HT1A receptors in brain. J. Nucl. Med. 48: 1154-1161, 2007.
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