Journal
NUCLEAR MEDICINE AND BIOLOGY
Volume 33, Issue 4, Pages 489-494Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.nucmedbio.2006.01.006
Keywords
CXCR4; peptide radiopharmaceutical; indium-111; metastatic tumor
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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. In-111-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, strormal cell-derived factor-1 alpha, to CXCR4 in a concentration-dependent manner with an IC50 of 7.9 nM (Ac-TZ14011: 1.2 nM). In biodistribution experiments, more In-111-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 (111)Wn-DTPA-Ac-TZ14011 would be a potential agent for the imaging of CXCR4 expression in metastatic tumors in vivo. (c) 2006 Elsevier Inc. All rights reserved.
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