TY - JOUR T1 - Disulfiram inhibits defluorination of [<sup>18</sup>F]FCWAY, reduces radioactivity in bone, and enhances visualization of binding to serotonin 5-HT<sub>1A</sub> receptors in human brain JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 61P LP - 61P VL - 48 IS - supplement 2 AU - Yong Hoon Ryu AU - Jeih-San Liow AU - Sami Zoghbi AU - Masahiro Fujita AU - Jerry Collins AU - Janet Sangare AU - Jinsoo Hong AU - Victor Pike AU - Robert Innis Y1 - 2007/05/01 UR - http://jnm.snmjournals.org/content/48/supplement_2/61P.1.abstract N2 - 202 Objectives: [18F]Trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-N-(2-pyridyl) cyclohexanecarboxamide ([18F]FCWAY) is a PET radioligand for 5-HT1A receptors. [18F]FCWAY undergoes significant defluorination with high radioactive uptake in skull, causing spillover contamination of underlying neocortex. The cytochrome P450 enzyme CYP2E1 catalyzes the defluorination of many drugs. We previously showed that miconazole, an inhibitor of CYP2E1, blocks radiodefluroination of FCWAY in rats (JNM,47:345, 2006). Here we used FCWAY to test the ability of the less toxic agent disulfiram to inhibit defluorination in man. Methods: Eight healthy volunteers had a PET scan before and after administration of 500 mg disulfiram (n = 6) or 2,000 mg cimetidine (n = 2). Seven of the subjects had arterial blood sampling during both scans. Results: Although cimetidine had relatively small and variable effects in two subjects, disulfiram reduced skull radioactivity by ~70% and increased brain uptake by about 50% (n = 5). Disulfiram decreased plasma free [18F]fluoride (mean peak level of 340±62% vs 62±43% SUV; p&lt;0.01) and increased the concentration of the parent [18F]FCWAY (with clearance decreasing from 14.8±7.8 to 7.9±2.8 L/h; p&lt;0.05). Using compartmental modeling with input of both [18F]FCWAY and the radiometabolite [18F]FC (trans-4-fluoro-cyclohexanecarboxylic acid), distribution volumes attributed to the parent radioligand unexpectedly decreased 40 – 60% after disulfiram, but the accuracy of the radiometabolite correction is uncertain. Conclusions: A single oral dose of disulfiram inhibited about 70% of the defluorination of [18F]FCWAY, increased the plasma concentration of FCWAY, increased brain uptake of activity, and resulted in better visualization of 5-HT1A receptors. Disulfiram is a safe and well tolerated drug that could be used for other radioligands that undergo defluorination via CYP2E1. ER -