RT Journal Article
SR Electronic
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
FD Society of Nuclear Medicine
SP 61P
OP 61P
VO 48
IS supplement 2
A1 Yong Hoon Ryu
A1 Jeih-San Liow
A1 Sami Zoghbi
A1 Masahiro Fujita
A1 Jerry Collins
A1 Janet Sangare
A1 Jinsoo Hong
A1 Victor Pike
A1 Robert Innis
YR 2007
UL http://jnm.snmjournals.org/content/48/supplement_2/61P.1.abstract
AB 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.