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In Vivo Near-infrared Fluorescence Imaging of Carcinoembryonic Antigen–expressing Tumor Cells in Mice¹

¹ From the Institute for Diagnostic and Interventional Radiology, Friedrich-Schiller-University Jena, FZL Erlanger Allee 101, D-07747 Jena, Germany (M.R.L., A.G., C.T., W.A.K., I.H.); and Federal Institute for Materials Research and Testing (BAM), Working Group Optical Spectroscopy, Berlin, Germany (J.P., U.R.). Received January 18, 2007; revision requested March 22; revision received July 17; accepted August 17; final version accepted October 29. Supported by Doktor-Robert-Pfleger Foundation. Address correspondence to I.H. (e-mail: Ingrid.Hilger{at}med.uni-jena.de).

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.

© RSNA, 2008