Junchao Tong, Alan A Wilson, Isabelle Boileau, Sylvain Houle, Stephen J Kish
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Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats: VMAT2 binding is sensitive to changes in vesicular dopamine concentration.
Binding of (+)-[11C]DTBZ (dihydrotetrabenazine) to the striatal vesicular monoamine transporter (VMAT2) is widely considered to be a stable marker of dopamine neurone integrity. However, we now find that specific binding of a tracer dose of (+)-[11C]DTBZ is modestly increased in rat striatum following dopamine depletion with alpha-methyl-p-tyrosine (alpha-MPT, +14%) or d-amphetamine (d-AMPH, 20 mg/kg, +12%) and decreased following dopamine elevation with gamma-hydroxybutyrate (GHB, -16%) or levodopa (-20%). We suggest that in vivo (+)-[11C]DTBZ binding in imaging studies is subject to competition by vesicular dopamine and, in this respect, is not a "stable" dopamine biomarker as is generally assumed.
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