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 Scopus citations


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
Issue number24
Publication statusPublished - Dec 15 2014



  • 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

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