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Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors.

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.

journal_name

Nucl Med Biol

journal_title

Nuclear medicine and biology

authors

Hanaoka H,Mukai T,Tamamura H,Mori T,Ishino S,Ogawa K,Iida Y,Doi R,Fujii N,Saji H

doi

10.1016/j.nucmedbio.2006.01.006

subject

Has Abstract

pub_date

2006-05-01 00:00:00

pages

489-94

issue

4

eissn

0969-8051

issn

1872-9614

pii

S0969-8051(06)00008-4

journal_volume

33

pub_type

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