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In Vivo Near-infrared Fluorescence Imaging of Carcinoembryonic Antigen-expressing Tumor Cells in Mice

  • 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-CEA–DY-676) and a low-affinity fluorescent probe (FabIgG–DY-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: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-CEA–DY-676) and a low-affinity fluorescent probe (FabIgG–DY-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 3.0–3.5 for both probes. In vitro experiments revealed the specific binding of the anti-CEA–DY-676 probe on CEA-expressing cells as compared with CEA-nonexpressing cells; the FabIgG–DY-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-CEA–DY-676 but not with that of the FabIgG–DY-676 at different times (2–24 hours, P < .005) after intravenous injection of the probes. Semiquantitative analysis revealed maximal fluorescence signals of anti-CEA–DY-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-CEA–DY-676 for specific NIRF imaging in in vivo tumor diagnosis.zeige mehrzeige weniger

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Metadaten
Autor*innen:M.-R. Lisy, A. Goermar, C. Thomas, Jutta Pauli, Ute Resch-GengerORCiD, W.A. Kaiser, I. Hilger
Dokumenttyp:Zeitschriftenartikel
Veröffentlichungsform:Verlagsliteratur
Sprache:Englisch
Titel des übergeordneten Werkes (Englisch):Radiology
Jahr der Erstveröffentlichung:2008
Herausgeber (Institution):International Society of Radiology
Verlag:Radiological Society of North America
Verlagsort:Oak Brook, Ill.
Jahrgang/Band:247
Ausgabe/Heft:3
Erste Seite:779
Letzte Seite:787
Freie Schlagwörter:Antibogy fragment arcitumomab; Carcinoembryonic antigen; Fluorescence spectroscopy; NIR fluorescent dye; NIRF imaging
DOI:10.1148/radiol.2472070123
ISSN:0033-8419
ISSN:1527-1315
Verfügbarkeit des Dokuments:Physisches Exemplar in der Bibliothek der BAM vorhanden ("Hardcopy Access")
Bibliotheksstandort:Sonderstandort: Publica-Schrank
Datum der Freischaltung:19.02.2016
Referierte Publikation:Ja
Datum der Eintragung als referierte Publikation:23.06.2008
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