Development of a 111In-labeled peptide derivative targeting a chemokine receptor, CXCR4, for imaging tumors.
Nucl Med Biol
; 33(4): 489-94, 2006 May.
Article
em En
| MEDLINE
| ID: mdl-16720240
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
/
Peptídeos Cíclicos
/
Biomarcadores Tumorais
/
Ácido Pentético
/
Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nucl Med Biol
Assunto da revista:
BIOLOGIA
/
MEDICINA NUCLEAR
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Japão