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

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:24

Article

Kumar, Amit¹  Lo, Su-Tang¹  Oez, Orhan K.¹  Sun, Xiankai^1,2 

[1] Univ Texas SW Med Ctr Dallas, Dept Radiol, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Adv Imaging Res Ctr, Dallas, TX 75390 USA

关键词: Positron emission tomography;    VMAT2;    Copper-64;    Bifunctional chelator;   

DOI  :  10.1016/j.bmcl.2014.10.070

来源: Elsevier

【 摘 要 】

Dihydrotetrabenazine (DTBZ) derivatized from (+) Tetrabenazine (TBZ) has been used for imaging the expression of VMAT2 when labeled with C-11 (t(1/2) = 20.3 min) or F-18 (t(1/2) = 110 min) in neurodegenerative diseases or pancreatic beta-cell. Because C-11 or F-18 radiolabels are only available in the proximity of a biomedical cyclotron facility, here we report our work of derivatizing (+) and (-) DTBZ using a Cu-64-specific bifunctional chelator scaffold (Cu-64: t(1/2) = 12.7 h) for the preparation of long-lived VMAT2 targeted radiotracers, Cu-64-CB-TE2A-(+)-DTBZ and Cu-64-CB-TE2A-(-)-DTBZ. The specific VMAT2 binding affinity of Cu-64-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 C-11 or F-18 labeled (+/-) DTBZ. (C) 2014 Elsevier Ltd. All rights reserved.

【 授权许可】

Free