A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging

Kohei Sano; Ryo Masuda; Hayato Hisada; Shinya Oishi; Kenta Shimokawa; Masahiro Ono; Nobutaka Fujii; Hideo Saji; Takahiro Mukai

doi:10.1016/j.bmcl.2014.01.031

A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging

Kohei Sano, Ryo Masuda, Hayato Hisada, Shinya Oishi, Kenta Shimokawa, Masahiro Ono, Nobutaka Fujii, Hideo Saji, Takahiro Mukai^*

^*Corresponding author for this work

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

5 Citations (Scopus)

Abstract

We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. ⁶⁷Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with ⁶⁷Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.

Original language	English
Pages (from-to)	1386-1388
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2014.01.031
Publication status	Published - 2014 Mar 1
Externally published	Yes

Keywords

Bivalent effect
CXCR4
DOTA
Radiogallium

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2014.01.031

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title = "A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging",

abstract = "We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. 67Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with 67Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.",

keywords = "Bivalent effect, CXCR4, DOTA, Radiogallium",

author = "Kohei Sano and Ryo Masuda and Hayato Hisada and Shinya Oishi and Kenta Shimokawa and Masahiro Ono and Nobutaka Fujii and Hideo Saji and Takahiro Mukai",

note = "Funding Information: We would like to thank FUJIFILM RI Pharma Co., Ltd, Tokyo, Japan , for donating 67 GaCl 3 . This work was supported in part by a Grant-in-Aid for Scientific Research (B) ( 21390347 ), a Grant-in-Aid for Scientific Research on Priority Areas from the Japan Society for the Promotion of Science , and the Project to Develop {\textquoteleft}Innovative Seeds{\textquoteright} of the Japan Science and Technology Agency . R.M. is grateful for Research Fellowships from the JSPS for Young Scientists . ",

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doi = "10.1016/j.bmcl.2014.01.031",

language = "English",

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pages = "1386--1388",

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T1 - A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging

AU - Sano, Kohei

AU - Masuda, Ryo

AU - Hisada, Hayato

AU - Oishi, Shinya

AU - Shimokawa, Kenta

AU - Ono, Masahiro

AU - Fujii, Nobutaka

AU - Saji, Hideo

AU - Mukai, Takahiro

N1 - Funding Information: We would like to thank FUJIFILM RI Pharma Co., Ltd, Tokyo, Japan , for donating 67 GaCl 3 . This work was supported in part by a Grant-in-Aid for Scientific Research (B) ( 21390347 ), a Grant-in-Aid for Scientific Research on Priority Areas from the Japan Society for the Promotion of Science , and the Project to Develop ‘Innovative Seeds’ of the Japan Science and Technology Agency . R.M. is grateful for Research Fellowships from the JSPS for Young Scientists .

PY - 2014/3/1

Y1 - 2014/3/1

N2 - We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. 67Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with 67Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.

AB - We have developed a novel radiogallium (Ga)-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging. A CXCR4 imaging probe with two CXCR4 antagonists (Ac-TZ14011) on Ga-DOTA core, Ga-DOTA-TZ2, was synthesized, and the affinity and binding to CXCR4 was evaluated in CXCR4 expressing cells in vitro. The affinity of Ga-DOTA-TZ2 for CXCR4 was 20-fold greater than the corresponding monovalent probe, Ga-DOTA-TZ1. 67Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with 67Ga-DOTA-TZ1, suggesting the bivalent effect enhances its binding to CXCR4. The incorporation of two CXCR4 antagonists to Ga-DOTA could be effective in detecting CXCR4-expressing tumors.

KW - Bivalent effect

KW - CXCR4

KW - DOTA

KW - Radiogallium

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A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging

Abstract

Keywords

ASJC Scopus subject areas

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