Carbon-11 labeled (+)DTBZ(right) and fluorine-18 labeled fluoropropylated (+)DTBZ(left)Reconstructed data from PET scan of healthy human brain using [18F]Fluoropropyl-DTBZ indicating
VMAT2 distribution[2]
[11C]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.[3] There are two
enantiomers of alpha-dihydrotetrabenazine, and the
dextrorotary(or (+) isomer) has a high
affinity of about 1 nanomolar Ki whereas the
levorotary (or (-) isomer) has approximately 1000 fold lower affinity with a Ki of about 2 micromolar.[4]
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.[5] Moreover, the VMAT2 density as determined by [18F]DTBZ has been shown to be well, inversely correlated with the severity of
Parkinson's disease.[6]
Avid Radiopharmaceuticals has sponsored clinical trials of [18F]AV-133 (or [18F]Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration.[7]
^Kilbourn, M; Lee, L; Vander Borght, T; Jewett, D; Frey, K (24 May 1995). "Binding of alpha-dihydrotetrabenazine to the vesicular monoamine transporter is stereospecific". European Journal of Pharmacology. 278 (3): 249–52.
doi:
10.1016/0014-2999(95)00162-e.
PMID7589162.