New Macrobicyclic Chelator for the Development of Ultrastable Cu-64-Radiolabeled Bioconjugate

作者：Pandya Darpan N; Dale Ajit V; Kim Jung Young; Lee Hochun; Ha Yeong Su; An Gwang Il; Yoo Jeongsoo^*

来源：Bioconjugate Chemistry, 2012, 23(3): 330-335.

DOI：10.1021/bc200539t

Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable Cu-64 complexes. However, its usefulness as a bifunctional chelator is limited because of its harsh radiolabeling conditions. Herein, we report new cross-bridged cyclam chelator for the development of ultrastable Cu-64-radiolabeled bioconjugates. Propylene cross-bridged TE2A (PCB-TE2A) was successfully synthesized in an efficient way. The Cu(II) complex of PCB-TE2A exhibited much higher kinetic stability than ECB-TE2A in acid decomplexation studies, and also showed high resistance to reduction-mediated demetalation. Furthermore, the quantitative radiolabeling of PCB-TE2A with Cu-64 was achieved under milder conditions compared to ECB-TE2A Biodistribution studies strongly indicate that the Cu-64 complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.

• 出版日期2012-3