title: New macrobicyclic chelator for the development of ultrastable 64Cu-radiolabeled bioconjugate.
abstract: Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable (64)Cu 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 (64)Cu-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 (64)Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the (64)Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.
authors.affiliation: Department of Molecular Medicine, Kyungpook National University, Daegu 700-422, South Korea.
authors.forename: Darpan N
authors.initials: DN
authors.lastname: Pandya
authors.forename: Ajit V
authors.initials: AV
authors.lastname: Dale
authors.forename: Jung Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Hochun
authors.initials: H
authors.lastname: Lee
authors.forename: Yeong Su
authors.initials: YS
authors.lastname: Ha
authors.forename: Gwang Il
authors.initials: GI
authors.lastname: An
authors.forename: Jeongsoo
authors.initials: J
authors.lastname: Yoo
mesh_terms: D000818:Animals; D002614:Chelating Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003301:Copper Radioisotopes / Q000737:chemistry*; D047028:Macrocyclic Compounds / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
chemical_list: D002614:Chelating Agents; D003301:Copper Radioisotopes; D047028:Macrocyclic Compounds