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 (11)C (t1/2=20.3 min) or (18)F (t1/2=110 min) in neurodegenerative diseases or pancreatic beta-cell. Because (11)C or (18)F radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a (64)Cu-specific bifunctional chelator scaffold ((64)Cu: t1/2=12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, (64)Cu-CB-TE2A-(+)-DTBZ and (64)Cu-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of (64)Cu-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 (11)C or (18)F labeled (±) DTBZ.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Su-Tang
authors.initials: ST
authors.lastname: Lo
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Orhan K
authors.initials: OK
authors.lastname: Öz
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xiankai
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D003301:Copper Radioisotopes; D003952:Diagnostic Imaging; D050417:Insulin-Secreting Cells / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000737:chemistry; D051381:Rats; D013552:Swine; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000737:chemistry; D050493:Vesicular Monoamine Transport Proteins / Q000378:metabolism*
chemical_list: D003301:Copper Radioisotopes; D019275:Radiopharmaceuticals; D050493:Vesicular Monoamine Transport Proteins; C032811:dihydrotetrabenazine; D013747:Tetrabenazine
keywords: Bifunctional chelator; Copper-64; Positron emission tomography; VMAT2