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 111In-labeling, diethylenetriaminepentaacetic acid ( DTPA) was attached to the side chain of d-Lys(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-1alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more 111In-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 111In-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo.
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Authors | Hirofumi Hanaoka, Takahiro Mukai, Hirokazu Tamamura, Tomohiko Mori, Seigo Ishino, Kazuma Ogawa, Yasuhiko Iida, Ryuichiro Doi, Nobutaka Fujii, Hideo Saji |
Journal | Nuclear medicine and biology
(Nucl Med Biol)
Vol. 33
Issue 4
Pg. 489-94
(May 2006)
ISSN: 0969-8051 [Print] United States |
PMID | 16720240
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 111indium-DTPA-Ac-TZ14011
- Biomarkers, Tumor
- Neoplasm Proteins
- Peptides
- Peptides, Cyclic
- Radiopharmaceuticals
- Receptors, Chemokine
- Pentetic Acid
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Topics |
- Animals
- Biomarkers, Tumor
(metabolism)
- Drug Delivery Systems
(methods)
- Drug Design
- Female
- Isotope Labeling
(methods)
- Metabolic Clearance Rate
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Neoplasm Proteins
(metabolism)
- Organ Specificity
- Pancreatic Neoplasms
(diagnostic imaging, metabolism)
- Pentetic Acid
(analogs & derivatives, chemistry, pharmacokinetics)
- Peptides
(chemical synthesis, pharmacokinetics)
- Peptides, Cyclic
(chemistry, pharmacokinetics)
- Radionuclide Imaging
- Radiopharmaceuticals
(chemical synthesis, pharmacokinetics)
- Receptors, Chemokine
(metabolism)
- Tissue Distribution
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