Abstract
The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For {sup 111}In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of D-Lys{sup 8} which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1{alpha}, to CXCR4 in a concentration-dependent manner with an IC{sub 5} of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more {sup 111}In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that {sup 111}In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.
Hanaoka, Hirofumi;
[1]
Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)];
Mukai, Takahiro;
[2]
Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)];
Tamamura, Hirokazu;
[1]
Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)];
Mori, Tomohiko;
[2]
Ishino, Seigo;
[1]
Ogawa, Kazuma;
[1]
Iida, Yasuhiko;
[3]
Doi, Ryuichiro;
[2]
Fujii, Nobutaka;
[1]
Saji, Hideo
[1]
- Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501 (Japan)
- Graduate School of Medicine, Kyoto University, Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)
- Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)
Citation Formats
Hanaoka, Hirofumi, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)], Mukai, Takahiro, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)], Tamamura, Hirokazu, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)], Mori, Tomohiko, Ishino, Seigo, Ogawa, Kazuma, Iida, Yasuhiko, Doi, Ryuichiro, Fujii, Nobutaka, and Saji, Hideo.
Development of a {sup 111}In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors.
United Kingdom: N. p.,
2006.
Web.
doi:10.1016/j.nucmedbio.2006.01.006.
Hanaoka, Hirofumi, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)], Mukai, Takahiro, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)], Tamamura, Hirokazu, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)], Mori, Tomohiko, Ishino, Seigo, Ogawa, Kazuma, Iida, Yasuhiko, Doi, Ryuichiro, Fujii, Nobutaka, & Saji, Hideo.
Development of a {sup 111}In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors.
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2006.01.006
Hanaoka, Hirofumi, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)], Mukai, Takahiro, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)], Tamamura, Hirokazu, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)], Mori, Tomohiko, Ishino, Seigo, Ogawa, Kazuma, Iida, Yasuhiko, Doi, Ryuichiro, Fujii, Nobutaka, and Saji, Hideo.
2006.
"Development of a {sup 111}In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors."
United Kingdom.
https://doi.org/10.1016/j.nucmedbio.2006.01.006.
@misc{etde_20837040,
title = {Development of a {sup 111}In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors}
author = {Hanaoka, Hirofumi, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)], Mukai, Takahiro, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)], Tamamura, Hirokazu, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)], Mori, Tomohiko, Ishino, Seigo, Ogawa, Kazuma, Iida, Yasuhiko, Doi, Ryuichiro, Fujii, Nobutaka, and Saji, Hideo}
abstractNote = {The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For {sup 111}In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of D-Lys{sup 8} which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1{alpha}, to CXCR4 in a concentration-dependent manner with an IC{sub 5} of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more {sup 111}In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that {sup 111}In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.}
doi = {10.1016/j.nucmedbio.2006.01.006}
journal = []
issue = {4}
volume = {33}
place = {United Kingdom}
year = {2006}
month = {May}
}
title = {Development of a {sup 111}In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors}
author = {Hanaoka, Hirofumi, Graduate School of Medicine, Gunma University, Showa-machi, Maebashi 371-8511 (Japan)], Mukai, Takahiro, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi, Higashi-ku, Fukuoka 812-8582 (Japan)], Tamamura, Hirokazu, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062 (Japan)], Mori, Tomohiko, Ishino, Seigo, Ogawa, Kazuma, Iida, Yasuhiko, Doi, Ryuichiro, Fujii, Nobutaka, and Saji, Hideo}
abstractNote = {The chemokine receptor CXCR4 is highly expressed in tumor cells and plays an important role in tumor metastasis. The aim of this study was to develop a radiopharmaceutical for the imaging of CXCR4-expressing tumors in vivo. Based on structure-activity relationships, we designed a 14-residue peptidic CXCR4 inhibitor, Ac-TZ14011, as a precursor for radiolabeled peptides. For {sup 111}In-labeling, diethylenetriaminepentaacetic acid (DTPA) was attached to the side chain of D-Lys{sup 8} which is distant from the residues indispensable for the antagonistic activity. In-DTPA-Ac-TZ14011 inhibited the binding of a natural ligand, stromal cell-derived factor-1{alpha}, to CXCR4 in a concentration-dependent manner with an IC{sub 5} of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more {sup 111}In-DTPA-Ac-TZ14011 accumulated in the CXCR4-expressing tumor than in blood or muscle. Furthermore, the tumor-to-blood and tumor-to-muscle ratios were significantly reduced by coinjection of Ac-TZ14011, indicating a CXCR4-mediated accumulation in tumor. These findings suggested that {sup 111}In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.}
doi = {10.1016/j.nucmedbio.2006.01.006}
journal = []
issue = {4}
volume = {33}
place = {United Kingdom}
year = {2006}
month = {May}
}