11C-Labeled Radiotracer for Noninvasive and Quantitative Assessment of the Thiocyanate Efflux System in the Brain

Thiocyanate (SCN-) alters the potency of certain agonists for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and dysfunctions in AMPA receptor signaling are considered to underlie a number of neurological diseases. While humans may be exposed to SCN(- )from the environment, including food sources, a carrier-mediated system transports SCN- from the brain into the blood and is an important regulator of SCN(- )distribution in the central nervous system. The assessment of this SCN- efflux system in the brain would thus be useful for understanding the mechanisms underlying the neurotoxicity of SCN(- )and for elucidating the relationship between the efflux system and brain diseases. However, the currently available technique for studying SCN- efflux is severely limited by its invasiveness. Here, we describe the development of a SCN(- )protracer, 9-pentyl-6-[C-11]thiocyanatopurine ([C-11]1), to overcome this limitation. [C-11]1 was synthesized by the reaction of the iodo-precursor and [C-11]SCN- or the reaction of the disulfide precursor with [C-11]NH4CN. The protracer [C-11]1 entered the brain after intravenous injection into mice and was rapidly metabolized to [C-11]SCN-, which was then eliminated from the brain. The efflux of [C-11]SCN- was dose-dependently inhibited by perchlorate, a monovalent anion, and the highest dose caused an 82% reduction in the efflux rate. Our findings demonstrate that [C-11]1 can be used for the noninvasive and quantitative assessment of the SCN(- )efflux system in the brain.