A new synthesis of TE2A-a potential bifunctional chelator for 64Cu

Darpan N. Pandya; Jung Young Kim; Wonjung Kwak; Jeong Chan Park; Manoj B. Gawande; Gwang Il An; Eun Kyoung Ryu; Jeongsoo Yoo

doi:10.1007/s13139-010-0031-2

A new synthesis of TE2A-a potential bifunctional chelator for ⁶⁴Cu

Darpan N. Pandya, Jung Young Kim, Wonjung Kwak, Jeong Chan Park, Manoj B. Gawande, Gwang Il An, Eun Kyoung Ryu, Jeongsoo Yoo

Department of Medicine

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

17 Scopus citations

Abstract

Purpose: The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. Methods: TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with ⁶⁴Cu and microPET imaging was performed to follow the clearance pattern of the ⁶⁴Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with ⁶⁴Cu. Results: TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that ⁶⁴Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with ⁶⁴Cu in 94% yield within 30 min. Conclusion: TE2A can be used by itself as a bifunctional chelator without any further structural modification.

Original language	English
Pages (from-to)	185-192
Number of pages	8
Journal	Nuclear Medicine and Molecular Imaging
Volume	44
Issue number	3
DOIs	https://doi.org/10.1007/s13139-010-0031-2
State	Published - Sep 2010

Keywords

Cu
Bifunctional chelator
Conjugation
RGD peptide
TE2A

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10.1007/s13139-010-0031-2

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title = "A new synthesis of TE2A-a potential bifunctional chelator for 64Cu",

abstract = "Purpose: The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. Methods: TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with 64Cu and microPET imaging was performed to follow the clearance pattern of the 64Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu. Results: TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that 64Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu in 94% yield within 30 min. Conclusion: TE2A can be used by itself as a bifunctional chelator without any further structural modification.",

keywords = "Cu, Bifunctional chelator, Conjugation, RGD peptide, TE2A",

author = "Pandya, {Darpan N.} and Kim, {Jung Young} and Wonjung Kwak and Park, {Jeong Chan} and Gawande, {Manoj B.} and An, {Gwang Il} and Ryu, {Eun Kyoung} and Jeongsoo Yoo",

year = "2010",

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doi = "10.1007/s13139-010-0031-2",

language = "English",

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pages = "185--192",

journal = "Nuclear Medicine and Molecular Imaging",

issn = "1869-3474",

publisher = "Springer Verlag",

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AU - Pandya, Darpan N.

AU - Kim, Jung Young

AU - Kwak, Wonjung

AU - Park, Jeong Chan

AU - Gawande, Manoj B.

AU - An, Gwang Il

AU - Ryu, Eun Kyoung

AU - Yoo, Jeongsoo

PY - 2010/9

Y1 - 2010/9

N2 - Purpose: The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. Methods: TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with 64Cu and microPET imaging was performed to follow the clearance pattern of the 64Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu. Results: TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that 64Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu in 94% yield within 30 min. Conclusion: TE2A can be used by itself as a bifunctional chelator without any further structural modification.

AB - Purpose: The development of a new bifunctional chelator, which holds radiometals strongly in living systems, is a prerequisite for the successful application of diseasespecific biomolecules to medical diagnosis and therapy. Recently, TE2A was reported to make kinetically more stable Cu(II) complexes than TETA. Herein, we report a new synthetic route to TE2A and explore its potential as a bifunctional chelator. Methods: TE2A was synthesized using the regioselective alkylation of benzyl bromoacetate and successive deprotection of the methylene bridge and benzyl group. Salt-free TE2A was radiolabeled with 64Cu and microPET imaging was performed to follow the clearance pattern of the 64Cu-TE2A complex. TE2A was conjugated with cyclic RGD peptide and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu. Results: TE2A was prepared in salt-free form from cyclam in an overall yield of 74%. The microPET images showed that 64Cu-TE2A is excreted rapidly from the body by the kidney and liver. TE2A was successfully conjugated with c(RGDyK) peptide through one carboxylate group and the TE2A-c(RGDyK) conjugate was radiolabeled with 64Cu in 94% yield within 30 min. Conclusion: TE2A can be used by itself as a bifunctional chelator without any further structural modification.

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KW - Conjugation

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EP - 192

JO - Nuclear Medicine and Molecular Imaging

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ER -

A new synthesis of TE2A-a potential bifunctional chelator for ⁶⁴Cu

Abstract

Keywords

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