Dopamine modulating drugs influence striatal (+)-[11C]DTBZ binding in rats:: VMAT2 binding is sensitive to changes in vesicular dopamine concentration

Binding of (+)-[(11)C]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 (+)-[(11)C]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 (+)-[(11)C]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.