Rat pancreas uptake of [11C]dihydrotetrabenazine stereoisomers.
(+)-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.
University of Michigan Medical School, Ann Arbor, MI 48109, USA. mkilbour@umich.edu
Michael R
MR
Kilbourn
D000818:Animals; D002250:Carbon Radioisotopes; D008297:Male; D010179:Pancreas / Q000378:metabolism*; D051381:Rats; D013237:Stereoisomerism; D013379:Substrate Specificity; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics
D002250:Carbon Radioisotopes; C032811:dihydrotetrabenazine; D013747:Tetrabenazine