Derivatization of (±) dihydrotetrabenazine for copper-64 labeling towards long-lived radiotracers for PET imaging of the vesicular monoamine transporter 2

Amit Kumar, Su Tang Lo, Orhan K. Öz, Xiankai Sun

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Dihydrotetrabenazine (DTBZ) derivatized from (+) Tetrabenazine (TBZ) has been used for imaging the expression of VMAT2 when labeled with 11C (t1/2 = 20.3 min) or 18F (t1/2 = 110 min) in neurodegenerative diseases or pancreatic beta-cell. Because 11C or 18F radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a 64Cu-specific bifunctional chelator scaffold (64Cu: t1/2 = 12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, 64Cu-CB-TE2A-(+)-DTBZ and 64Cu-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of 64Cu-CB-TE2A-(+)-DTBZ measured using rat brain homogenate or porcine islets was not compromised by our chemical modifications while that of its (-) counterpart remained low as in 11C or 18F labeled (±) DTBZ.

Original languageEnglish (US)
Pages (from-to)5663-5665
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume24
Issue number24
DOIs
StatePublished - Dec 15 2014

Fingerprint

Vesicular Monoamine Transport Proteins
Labeling
Copper
Imaging techniques
Tetrabenazine
Neurodegenerative diseases
Cyclotrons
Chemical modification
Insulin-Secreting Cells
Chelating Agents
Scaffolds
Neurodegenerative Diseases
dihydrotetrabenazine
Rats
Brain
Swine

Keywords

  • Bifunctional chelator
  • Copper-64
  • Positron emission tomography
  • VMAT2

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

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title = "Derivatization of (±) dihydrotetrabenazine for copper-64 labeling towards long-lived radiotracers for PET imaging of the vesicular monoamine transporter 2",
abstract = "Dihydrotetrabenazine (DTBZ) derivatized from (+) Tetrabenazine (TBZ) has been used for imaging the expression of VMAT2 when labeled with 11C (t1/2 = 20.3 min) or 18F (t1/2 = 110 min) in neurodegenerative diseases or pancreatic beta-cell. Because 11C or 18F radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a 64Cu-specific bifunctional chelator scaffold (64Cu: t1/2 = 12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, 64Cu-CB-TE2A-(+)-DTBZ and 64Cu-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of 64Cu-CB-TE2A-(+)-DTBZ measured using rat brain homogenate or porcine islets was not compromised by our chemical modifications while that of its (-) counterpart remained low as in 11C or 18F labeled (±) DTBZ.",
keywords = "Bifunctional chelator, Copper-64, Positron emission tomography, VMAT2",
author = "Amit Kumar and Lo, {Su Tang} and {\"O}z, {Orhan K.} and Xiankai Sun",
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AU - Kumar, Amit

AU - Lo, Su Tang

AU - Öz, Orhan K.

AU - Sun, Xiankai

PY - 2014/12/15

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N2 - Dihydrotetrabenazine (DTBZ) derivatized from (+) Tetrabenazine (TBZ) has been used for imaging the expression of VMAT2 when labeled with 11C (t1/2 = 20.3 min) or 18F (t1/2 = 110 min) in neurodegenerative diseases or pancreatic beta-cell. Because 11C or 18F radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a 64Cu-specific bifunctional chelator scaffold (64Cu: t1/2 = 12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, 64Cu-CB-TE2A-(+)-DTBZ and 64Cu-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of 64Cu-CB-TE2A-(+)-DTBZ measured using rat brain homogenate or porcine islets was not compromised by our chemical modifications while that of its (-) counterpart remained low as in 11C or 18F labeled (±) DTBZ.

AB - Dihydrotetrabenazine (DTBZ) derivatized from (+) Tetrabenazine (TBZ) has been used for imaging the expression of VMAT2 when labeled with 11C (t1/2 = 20.3 min) or 18F (t1/2 = 110 min) in neurodegenerative diseases or pancreatic beta-cell. Because 11C or 18F radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a 64Cu-specific bifunctional chelator scaffold (64Cu: t1/2 = 12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, 64Cu-CB-TE2A-(+)-DTBZ and 64Cu-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of 64Cu-CB-TE2A-(+)-DTBZ measured using rat brain homogenate or porcine islets was not compromised by our chemical modifications while that of its (-) counterpart remained low as in 11C or 18F labeled (±) DTBZ.

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