[11C]phenytoin revisited: synthesis by [11C]CO carbonylation and first evaluation as a P-gp tracer in rats.
2012 (English)In: EJNMMI Research, ISSN 2191-219X, Vol. 2, no 1, 36- p.Article in journal (Refereed) Published
ABSTRACT: BACKGROUND: At present, several positron emission tomography (PET) tracers are in use for imaging Pglycoprotein (P-gp) function in man. At baseline, substrate tracers such as R-[11C]verapamil display low brain concentrations with a distribution volume of around 1. [11C]phenytoin is supposed to be a weaker P-gp substrate, which may lead to higher brain concentrations at baseline. This could facilitate assessment of P-gp function when P-gp is upregulated. The purpose of this study was to synthesize [11C]phenytoin and to characterize its properties as a P-gp tracer. METHODS: [11C]CO was used to synthesize [11C]phenytoin by rhodium-mediated carbonylation. Metabolism and, using PET, brain pharmacokinetics of [11C]phenytoin were studied in rats. Effects of P-gp function on [11C]phenytoin uptake were assessed using predosing with tariquidar. RESULTS: [11C]phenytoin was synthesized via [11C]CO in an overall decay-corrected yield of 22 +/- 4%. At 45 min after administration, 19% and 83% of radioactivity represented intact [11C]phenytoin in the plasma and brain, respectively. Compared with baseline, tariquidar predosing resulted in a 45% increase in the cerebral distribution volume of [11C]phenytoin. CONCLUSIONS: Using [11C]CO, the radiosynthesis of [11C]phenytoin could be improved. [11C]phenytoin appeared to be a rather weak P-gp substrate.
Place, publisher, year, edition, pages
2012. Vol. 2, no 1, 36- p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-185289DOI: 10.1186/2191-219X-2-36PubMedID: 22747744OAI: oai:DiVA.org:uu-185289DiVA: diva2:571163