Filtern
Erscheinungsjahr
- 2008 (1) (entfernen)
Dokumenttyp
Sprache
- Englisch (1)
Referierte Publikation
- ja (1)
Schlagworte
- NIR fluorescent dye (1) (entfernen)
Purpose: To prospectively depict carcinoembryonic antigen (CEA)-expressing tumors in mice with a high-affinity probe consisting of a near-infrared (NIR) fluorochrome and the clinically used anti-CEA antibody fragment arcitumomab.
Materials and Methods: This study was approved by the regional animal committee. By coupling a NIR fluorescent (NIRF) cyanine dye (DY-676) to a specific antibody fragment directed against CEA (arcitumomab) and a nonspecific IgG Fab fragment, a bio-optical high-affinity fluorescent probe (anti-CEADY-676) and a low-affinity fluorescent probe (FabIgGDY-676) were designed. The dye-to-protein ratios were determined, and both probes were tested for NIRF imaging in vitro on CEA-expressing LS-174T human colonic adenocarcinoma cells and CEA-nonexpressing A-375 human melanoma cells by using a bio-optical NIR small-animal imager. In vivo data of xenografted LS-174T and A-375 tumors in mice (n = 10) were recorded and statistically analyzed (Student t test).
Results: The dye-to-protein ratios were determined as 3.03.5 for both probes. In vitro experiments revealed the specific binding of the anti-CEADY-676 probe on CEA-expressing cells as compared with CEA-nonexpressing cells; the FabIgGDY-676 probe showed a markedly lower binding affinity to cells. In vivo LS-174T tumors xenografted in all mice could be significantly distinguished from A-375 tumors with application of the anti-CEADY-676 but not with that of the FabIgGDY-676 at different times (224 hours, P < .005) after intravenous injection of the probes. Semiquantitative analysis revealed maximal fluorescence signals of anti-CEADY-676 to CEA-expressing tumors about 8 hours after injection.
Conclusion: Findings of this study indicate the potential use of the high-affinity probe anti-CEADY-676 for specific NIRF imaging in in vivo tumor diagnosis.