Novel 64Cu-radiolabeled bile acid conjugates for targeted PET imaging

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:25

Article

Chong, Hyun-Soon¹  Chen, Yunwei¹  Kang, Chi Soo¹  Sun, Xiang¹  Wu, Ningjie¹ 

[1] IIT, Dept Biol & Chem Sci, Div Chem, Chicago, IL 60616 USA

关键词: Bifunctional chelator;    Polyaminocarboxylate;    PET imaging;    Cu-64;    Bile acid;    Radiolabeling;    Serum stability;   

DOI  :  10.1016/j.bmcl.2015.01.008

来源: Elsevier

【 摘 要 】

A promising bifunctional chelate (N-NE3TA) was conjugated to bile acids, cholic acid (CA), deoxycholic acid (DCA), and chenodeoxycholic acid (CDCA) as tumor targeting vectors. Bile acid conjugates of N-NE3TA (CA-N-NE3TA, DCA-N-NE3TA, and CDCA-N-NE3TA) were comparatively evaluated for complexation with Cu-64, an imaging probe for positron emission tomography (PET). N-NE3TA-bile acid conjugates were evaluated for radiolabeling kinetics with Cu-64, and the corresponding Cu-64-radiolabeled conjugates were screened for complex stability in human serum and EDTA solution. The NE3TA-bile acid conjugates instantly bound to Cu-64 with excellent radiolabeling efficiency at room temperature. All NE3TA-bile acid conjugates radiolabeled with Cu-64 remained inert in human serum for 2 days without releasing a considerable amount of the radioactivity. The Cu-64-radiolabeled complexes were further challenged by EDTA in a 100-fold molar excess. Bile acid-N-NE3TA conjugates radiolabeled with Cu-64 were quite stable with a minimal transfer of Cu-64 to EDTA at 4 h time point. The in vitro data indicate that the bile acid-N-NE3TA conjugates deserve further biological evaluation for Cu-64-based targeted PET imaging applications. (C) 2015 Elsevier Ltd. All rights reserved.

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