New bifunctional chelator for 64Cu-immuno-positron emission tomography

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

doi:10.1021/bc400192a

New bifunctional chelator for ⁶⁴Cu-immuno-positron emission tomography

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

Department of Energy and Science and Engineering

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

22 Scopus citations

Abstract

A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH₂ complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with ⁶⁴Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the ⁶⁴Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by ⁶⁴Cu-immuno-positron emission tomography imaging in animal models.

Original language	English
Pages (from-to)	1356-1366
Number of pages	11
Journal	Bioconjugate Chemistry
Volume	24
Issue number	8
DOIs	https://doi.org/10.1021/bc400192a
State	Published - 21 Aug 2013

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10.1021/bc400192a

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@article{9324ccb3a9fe43c880c98806700aad30,

title = "New bifunctional chelator for 64Cu-immuno-positron emission tomography",

abstract = "A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron emission tomography imaging in animal models.",

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

year = "2013",

month = aug,

day = "21",

doi = "10.1021/bc400192a",

language = "English",

volume = "24",

pages = "1356--1366",

journal = "Bioconjugate Chemistry",

issn = "1043-1802",

publisher = "American Chemical Society",

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T1 - New bifunctional chelator for 64Cu-immuno-positron emission tomography

AU - Pandya, Darpan N.

AU - Bhatt, Nikunj

AU - Dale, Ajit V.

AU - Kim, Jung Young

AU - Lee, Hochun

AU - Ha, Yeong Su

AU - Lee, Ji Eun

AU - An, Gwang Il

AU - Yoo, Jeongsoo

PY - 2013/8/21

Y1 - 2013/8/21

N2 - A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron emission tomography imaging in animal models.

AB - A new tetraazamacrocyclic bifunctional chelator, TE2A-Bn-NCS, was synthesized in high overall yield from cyclam. An extra functional group (NCS) was introduced to the N-atom of TE2A for specific conjugation with antibody. The Cu complex of TE2A-Bn-NCS showed high kinetic stability in acidic decomplexation and cyclic voltammetry studies. X-ray structure determination of the Cu-TE2A-Bn-NH2 complex confirmed octahedral geometry, in which copper atom is strongly coordinated by four macrocyclic nitrogens in equatorial positions and two carboxylate oxygen atoms occupy the elongated axial positions. Trastuzumab was conjugated with TE2A-Bn-NCS and then radiolabeled with 64Cu quantitatively at room temperature within 10 min. Biodistribution studies showed that the 64Cu-labeled TE2A-Bn-NCS-trastuzumab conjugates maintain high stability in physiological conditions, and NIH3T6.7 tumors were clearly visualized up to 3 days by 64Cu-immuno-positron emission tomography imaging in animal models.

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U2 - 10.1021/bc400192a

DO - 10.1021/bc400192a

M3 - Article

C2 - 23883075

AN - SCOPUS:84883192247

SN - 1043-1802

VL - 24

SP - 1356

EP - 1366

JO - Bioconjugate Chemistry

JF - Bioconjugate Chemistry

IS - 8

ER -

New bifunctional chelator for ⁶⁴Cu-immuno-positron emission tomography

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