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IntroductionThere exists an efflux system for transporting thiocyanate from the brain to the blood, and this is an important factor controlling thiocyanate distribution in the brain. The assessment of the thiocyanate efflux system in the brain are expected to be useful for evaluating the neurotoxicity of thiocyanate and for studying the relationship between the efflux system and brain diseases. A 11C-labeled purine derivative has been recently developed for imaging the thiocyanate efflux system.1 This tracer was synthesized by the reaction of the iodo-precursor and [11C]thiocyanate or the reaction of the disulfide precursor with [11C]cyanide; however, the radiochemical yields were low.1 Here, we examined whether [11C]cyanide itself can be used for imaging the thiocyanate efflux system in the brain.MethodsThe preparation of [11C]cyanide using the traditional method was performed as previously reported.2 [11C]Cyanide was collected in phosphate-buffered saline after the gas product was passed through a column filled with KHSO4 to remove NH3. The time courses of the fraction of [11C]cyanide in mouse brain homogenate were examined, and the brain uptake was measured at 1, 5, and 15 min after intravenous administration of [11C]cyanide into mice. The chemical form in the brain at 5 min after intravenous administration was also analyzed by HPLC.Results[11C]Cyanide was stable in phosphate buffer, whereas it was converted to [11C]thiocyanate in mouse brain homogenates. The conversion rate was linearly dependent on the homogenate concentrations. [11C]Cyanide showed high uptake (ca. 9% ID/g tissue) in the brain 1 min after administration, and then a decrease in the next 15 min. By contrast, the uptake of [11C]thiocyanate from blood into the brain was lower than that of [11C]cyanide. Moreover, the radioactive compounds in the brain at 5 min postinjection of [11C]cyanide were found to be nearly completely composed of [11C]thiocyanate. The efflux rate of [11C]thiocyanate from the brain was comparable to that previously reported using the 11C-labeled purine derivative.1ConclusionsThese results suggest that 1) [11C]cyanide diffuses into the brain across the blood-brain barrier after intravenous administration, 2) it is rapidly metabolized to [11C]thiocyanate, and 3) this anion is then cleared from the brain. [11C]Cyanide may therefore allow the imaging of the thiocyanate efflux system in the brain. |
