Dihydrotetrabenazine or DTBZ is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

C₁₉H₂₉NO₃. It is a close analog of

tetrabenazine Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenaz ...

. DTBZ and its derivatives, when labeled with

positron The positron or antielectron is the antiparticle or the antimatter counterpart of the electron. It has an electric charge of +1 '' e'', a spin of 1/2 (the same as the electron), and the same mass as an electron. When a positron collides ...

emitting isotopes such as

carbon-11 Carbon (6C) has 15 known isotopes, from to , of which and are stable. The longest-lived radioisotope is , with a half-life of years. This is also the only carbon radioisotope found in nature—trace quantities are formed cosmogenically by ...

and

fluorine-18 Fluorine-18 (18F) is a fluorine radioisotope which is an important source of positrons. It has a mass of 18.0009380(6) u and its half-life is 109.771(20) minutes. It decays by positron emission 96% of the time and electron capture 4% of the time ...

, are used as

PET A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence, ...

radioligand A radioligand is a radioactive biochemical substance (in particular, a ligand that is radiolabeled) that is used for diagnosis or for research-oriented study of the receptor systems of the body. In a neuroimaging application the radioligand is inj ...

s for examining

VMAT2 The solute carrier family 18 member 2 (SLC18A2) also known as vesicular monoamine transporter 2 (VMAT2) is a protein that in humans is encoded by the ''SLC18A2'' gene. SLC18A2 is an integral membrane protein that transports monoamines—particul ...

Use in Positron Emission Tomography

sup>11CTBZ as a PET radioligand with affinity for VMAT2 was developed in the mid 1990s by

David E. Kuhl David Edmund Kuhl (October 27, 1929 in St. Louis, Missouri – May 28, 2017 in Ann Arbor, Michigan) was an Americans, American scientist specializing in nuclear medicine. He was well known for his pioneering work in positron emission tomography. ...

and colleagues at the

University of Michigan , mottoeng = "Arts, Knowledge, Truth" , former_names = Catholepistemiad, or University of Michigania (1817–1821) , budget = $10.3 billion (2021) , endowment = $17 billion (2021)As o ...

. There are two

enantiomers In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

of alpha-dihydrotetrabenazine, and the

dextrorotary Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

(or (+) isomer) has a high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Partn ...

of about 1 nanomolar K_i whereas the

levorotary Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

(or (-) isomer) has approximately 1000 fold lower affinity with a K_i of about 2 micromolar. VMAT2 is a membrane bound protein and a

biomarker In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, ...

for

Parkinson's disease Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...

. Binding of DTBZ to VMAT2 in individuals with

is significantly reduced. Moreover, the VMAT2 density as determined by sup>18FTBZ has been shown to be well, inversely correlated with the severity of

Avid Radiopharmaceuticals Avid Radiopharmaceuticals is an American company, founded by Dr. Daniel Skovronsky, and based at the University City Science Center research campus in Philadelphia, Pennsylvania. The company has developed a radioactive tracer called Florbetapir ( ...

has sponsored clinical trials of sup>18FV-133 (or sup>18Fluoropropyl-(+)-DTBZ) to identify subjects with dopaminergic degeneration.

References

{{Monoamine reuptake inhibitors Articles containing video clips Catechol ethers Monoamine-depleting agents University of Michigan VMAT inhibitors

Use in Positron Emission Tomography

See also

References