A radiogallium-DOTA-based bivalent peptidic ligand targeting a chemokine receptor, CXCR4, for tumor imaging.
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. (67)Ga-DOTA-TZ2 showed the significantly higher accumulation in CXCR4-expressing tumor cells compared with (67)Ga-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.
Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Kohei
K
Sano
Department of Bioorganic Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Ryo
R
Masuda
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Hayato
H
Hisada
Department of Bioorganic Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Shinya
S
Oishi
Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kenta
K
Shimokawa
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Masahiro
M
Ono
Department of Bioorganic Medical Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Nobutaka
N
Fujii
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida Shimoadachimachi, Sakyo-ku, Kyoto 606-8501, Japan.
Hideo
H
Saji
Department of Biomolecular Recognition Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Biophysical Chemistry, Kobe Pharmaceutical University, 4-19-1 Motoyama Kitamachi, Higashinada-ku, Kobe 658-8558, Japan. Electronic address: tmukai@kobepharma-u.ac.jp.
Takahiro
T
Mukai
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005710:Gallium Radioisotopes / Q000737:chemistry; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry*; D008024:Ligands; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005710:Gallium Radioisotopes; D006573:Heterocyclic Compounds, 1-Ring; D008024:Ligands; D010455:Peptides; D019275:Radiopharmaceuticals; D019718:Receptors, CXCR4; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Bivalent effect; CXCR4; DOTA; Radiogallium