Dihydrotetrabenazine
Dihydrotetrabenazine or DTBZ is an organic compound with the chemical formula C19H29NO3. It is a close analog of tetrabenazine. DTBZ and its derivatives, when labeled with positron emitting isotopes such as carbon-11 and fluorine-18, are used as PET radioligands for examining VMAT2.DTBZ as a PET radioligand with affinity for VMAT2 was developed in the mid 1990s by David E. Kuhl and colleagues at the University of Michigan. There are two enantiomers of alpha-dihydrotetrabenazine, and the dextrorotary has a high affinity of about 1 nanomolar Ki whereas the levorotary has approximately 1000 fold lower affinity with a Ki of about 2 micromolar.
VMAT2 is a membrane bound protein and a biomarker for Parkinson's disease. Binding of DTBZ to VMAT2 in individuals with Parkinson's disease is significantly reduced. Moreover, the VMAT2 density as determined by DTBZ has been shown to be well, inversely correlated with the severity of Parkinson's disease.
Avid Radiopharmaceuticals has sponsored clinical trials of AV-133 to identify subjects with dopaminergic degeneration.
