Rat pancreas uptake of [11C]dihydrotetrabenazine stereoisomers

Abstract

(+)-α-[(11)C]Dihydrotetrabenazine ((+)-[(11)C]DTBZ), a radioligand for the vesicular monoamine transporter type 2 (VMAT2), has been previously proposed as an in vivo marker of beta-cell degeneration in the pancreas. The stereospecificity of uptake of [(11)C]DTBZ into rat pancreas was examined here using radiolabeled forms of the (+)- and (-)-isomers. Pancreas localization of (+)-[(11)C]DTBZ could be partially blocked by prior administration of unlabeled (+)-DTBZ. Pancreatic uptake of the (-)-isomer was unexpectedly high and could not be blocked by pretreatment with (+)-DTBZ, but could be significantly reduced by treatment with racemic tetrabenazine, an in vivo source of (-)-DTBZ. These studies indicate that the inactive isomer of DTBZ does not provide a mechanism for defining the nonspecific binding of (+)-DTBZ in rat pancreas.