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

将(±)二氢四苯嗪衍生化,用于铜-64标记,制备用于PET成像囊泡单胺转运蛋白2的长寿命放射性示踪剂

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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.

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