Development of new peptide-based chelating agents for site-specific radiolabeling with 64Cu

Takaaki Miyamoto, Shinichiro Kamino, Akira Odani, Makoto Hiromura, Shuichi Enomoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Radiolabeled monoclonal antibodies (mAbs) are very useful molecular probes for nuclear imaging technique due to their high-target specificity and high-stability in the bloodstream. MAbs are generally labeled by indirect method using the combination of relatively long-lived metallic radionuclides (including 64Cu, 89Zr, and 111In) and bifunctional chelating agents which are capable of binding both antibodies and radio metals. The indirect radiolabeling method has some advantages such as high labeling efficiency and long-term retention ability within their target cells. However, this conventional labeling method can potentially lead to low-target affinity of the mAb probes, because of the non-site-specific introduction of the bifunctional chelators into the active site of the mAbs. To overcome the shortcoming, we proposed a new direct labeling method utilizing fusion proteins comprising mAbs linked to metal binding peptides at the N- or C-terminus. In this study, we synthesized new peptide derivatives possessing an N-terminal tripeptide sequence (Xaa-Yaa-His) called the amino terminal Cu2+- and Ni2+-binding (ATCUN) motif as 64Cu binding peptides for the proposed labeling method. Moreover, we studied the stability constants of Cu2+-ATCUN peptide complexes by pH titration. From these studies, we found that a low basicity of the N-terminal amine in the peptide resulted in a high stability constant of the complex. This finding may provide valuable guidelines in designing the ATCUN peptide with high-binding affinity toward 64Cu.

Original languageEnglish
Pages (from-to)797-800
Number of pages4
JournalYakugaku Zasshi
Volume134
Issue number7
DOIs
Publication statusPublished - 2014
Externally publishedYes

Fingerprint

Chelating Agents
Peptides
Monoclonal Antibodies
Metals
Molecular Probes
Radio
Radioisotopes
Amines
Catalytic Domain
Guidelines
Antibodies
Proteins

Keywords

  • Copper-64
  • Nuclear imaging
  • Radiolabeling

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Medicine(all)

Cite this

Development of new peptide-based chelating agents for site-specific radiolabeling with 64Cu. / Miyamoto, Takaaki; Kamino, Shinichiro; Odani, Akira; Hiromura, Makoto; Enomoto, Shuichi.

In: Yakugaku Zasshi, Vol. 134, No. 7, 2014, p. 797-800.

Research output: Contribution to journalArticle

Miyamoto, Takaaki ; Kamino, Shinichiro ; Odani, Akira ; Hiromura, Makoto ; Enomoto, Shuichi. / Development of new peptide-based chelating agents for site-specific radiolabeling with 64Cu. In: Yakugaku Zasshi. 2014 ; Vol. 134, No. 7. pp. 797-800.
@article{333eb804169c45dc9f05f61a03851618,
title = "Development of new peptide-based chelating agents for site-specific radiolabeling with 64Cu",
abstract = "Radiolabeled monoclonal antibodies (mAbs) are very useful molecular probes for nuclear imaging technique due to their high-target specificity and high-stability in the bloodstream. MAbs are generally labeled by indirect method using the combination of relatively long-lived metallic radionuclides (including 64Cu, 89Zr, and 111In) and bifunctional chelating agents which are capable of binding both antibodies and radio metals. The indirect radiolabeling method has some advantages such as high labeling efficiency and long-term retention ability within their target cells. However, this conventional labeling method can potentially lead to low-target affinity of the mAb probes, because of the non-site-specific introduction of the bifunctional chelators into the active site of the mAbs. To overcome the shortcoming, we proposed a new direct labeling method utilizing fusion proteins comprising mAbs linked to metal binding peptides at the N- or C-terminus. In this study, we synthesized new peptide derivatives possessing an N-terminal tripeptide sequence (Xaa-Yaa-His) called the amino terminal Cu2+- and Ni2+-binding (ATCUN) motif as 64Cu binding peptides for the proposed labeling method. Moreover, we studied the stability constants of Cu2+-ATCUN peptide complexes by pH titration. From these studies, we found that a low basicity of the N-terminal amine in the peptide resulted in a high stability constant of the complex. This finding may provide valuable guidelines in designing the ATCUN peptide with high-binding affinity toward 64Cu.",
keywords = "Copper-64, Nuclear imaging, Radiolabeling",
author = "Takaaki Miyamoto and Shinichiro Kamino and Akira Odani and Makoto Hiromura and Shuichi Enomoto",
year = "2014",
doi = "10.1248/yakushi.14-00017-4",
language = "English",
volume = "134",
pages = "797--800",
journal = "Yakugaku Zasshi",
issn = "0031-6903",
publisher = "Pharmaceutical Society of Japan",
number = "7",

}

TY - JOUR

T1 - Development of new peptide-based chelating agents for site-specific radiolabeling with 64Cu

AU - Miyamoto, Takaaki

AU - Kamino, Shinichiro

AU - Odani, Akira

AU - Hiromura, Makoto

AU - Enomoto, Shuichi

PY - 2014

Y1 - 2014

N2 - Radiolabeled monoclonal antibodies (mAbs) are very useful molecular probes for nuclear imaging technique due to their high-target specificity and high-stability in the bloodstream. MAbs are generally labeled by indirect method using the combination of relatively long-lived metallic radionuclides (including 64Cu, 89Zr, and 111In) and bifunctional chelating agents which are capable of binding both antibodies and radio metals. The indirect radiolabeling method has some advantages such as high labeling efficiency and long-term retention ability within their target cells. However, this conventional labeling method can potentially lead to low-target affinity of the mAb probes, because of the non-site-specific introduction of the bifunctional chelators into the active site of the mAbs. To overcome the shortcoming, we proposed a new direct labeling method utilizing fusion proteins comprising mAbs linked to metal binding peptides at the N- or C-terminus. In this study, we synthesized new peptide derivatives possessing an N-terminal tripeptide sequence (Xaa-Yaa-His) called the amino terminal Cu2+- and Ni2+-binding (ATCUN) motif as 64Cu binding peptides for the proposed labeling method. Moreover, we studied the stability constants of Cu2+-ATCUN peptide complexes by pH titration. From these studies, we found that a low basicity of the N-terminal amine in the peptide resulted in a high stability constant of the complex. This finding may provide valuable guidelines in designing the ATCUN peptide with high-binding affinity toward 64Cu.

AB - Radiolabeled monoclonal antibodies (mAbs) are very useful molecular probes for nuclear imaging technique due to their high-target specificity and high-stability in the bloodstream. MAbs are generally labeled by indirect method using the combination of relatively long-lived metallic radionuclides (including 64Cu, 89Zr, and 111In) and bifunctional chelating agents which are capable of binding both antibodies and radio metals. The indirect radiolabeling method has some advantages such as high labeling efficiency and long-term retention ability within their target cells. However, this conventional labeling method can potentially lead to low-target affinity of the mAb probes, because of the non-site-specific introduction of the bifunctional chelators into the active site of the mAbs. To overcome the shortcoming, we proposed a new direct labeling method utilizing fusion proteins comprising mAbs linked to metal binding peptides at the N- or C-terminus. In this study, we synthesized new peptide derivatives possessing an N-terminal tripeptide sequence (Xaa-Yaa-His) called the amino terminal Cu2+- and Ni2+-binding (ATCUN) motif as 64Cu binding peptides for the proposed labeling method. Moreover, we studied the stability constants of Cu2+-ATCUN peptide complexes by pH titration. From these studies, we found that a low basicity of the N-terminal amine in the peptide resulted in a high stability constant of the complex. This finding may provide valuable guidelines in designing the ATCUN peptide with high-binding affinity toward 64Cu.

KW - Copper-64

KW - Nuclear imaging

KW - Radiolabeling

UR - http://www.scopus.com/inward/record.url?scp=84907291619&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84907291619&partnerID=8YFLogxK

U2 - 10.1248/yakushi.14-00017-4

DO - 10.1248/yakushi.14-00017-4

M3 - Article

VL - 134

SP - 797

EP - 800

JO - Yakugaku Zasshi

JF - Yakugaku Zasshi

SN - 0031-6903

IS - 7

ER -