New macrobicyclic chelator for the development of ultrastable 64Cu-radiolabeled bioconjugate

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

doi:10.1021/bc200539t

New macrobicyclic chelator for the development of ultrastable ⁶⁴Cu-radiolabeled bioconjugate

Darpan N. Pandya, Ajit V. Dale, Jung Young Kim, Hochun Lee, Yeong Su Ha, Gwang Il An, Jeongsoo Yoo

Department of Medicine

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable ⁶⁴Cu 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 ⁶⁴Cu-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 ⁶⁴Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the ⁶⁴Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.

Original language	English
Pages (from-to)	330-335
Number of pages	6
Journal	Bioconjugate Chemistry
Volume	23
Issue number	3
DOIs	https://doi.org/10.1021/bc200539t
State	Published - 21 Mar 2012

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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 64Cu 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 64Cu-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 64Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the 64Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.",

author = "Pandya, {Darpan N.} and Dale, {Ajit V.} and Kim, {Jung Young} and Hochun Lee and Ha, {Yeong Su} and An, {Gwang Il} and Jeongsoo Yoo",

year = "2012",

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doi = "10.1021/bc200539t",

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T1 - New macrobicyclic chelator for the development of ultrastable 64Cu-radiolabeled bioconjugate

AU - Pandya, Darpan N.

AU - Dale, Ajit V.

AU - Kim, Jung Young

AU - Lee, Hochun

AU - Ha, Yeong Su

AU - An, Gwang Il

AU - Yoo, Jeongsoo

PY - 2012/3/21

Y1 - 2012/3/21

N2 - Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable 64Cu 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 64Cu-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 64Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the 64Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.

AB - Ethylene cross-bridged cyclam with two acetate pendant arms, ECB-TE2A, is known to form the most kinetically stable 64Cu 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 64Cu-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 64Cu was achieved under milder conditions compared to ECB-TE2A. Biodistribution studies strongly indicate that the 64Cu complexes of PCB-TE2A cleared out rapidly from the body with minimum decomplexation.

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JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

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ER -

New macrobicyclic chelator for the development of ultrastable ⁶⁴Cu-radiolabeled bioconjugate

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