Journal of Experimental Medicine, Vol 158, 413-427, Copyright © 1983 by Rockefeller University Press

ARTICLES

Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice

F Buchegger, CM Haskell, M Schreyer, BR Scazziga, S Randin, S Carrel and JP Mach

Four monoclonal antibodies against carcinoembryonic antigen (CEA) have been selected from 32 hybrids that produce antibodies against this antigen, by the criteria of high affinity for CEA and low cross- reactivity with granulocyte glycoprotein(s). The specificity of tumor localization in vivo of the four MAb, and their F(ab')2 and Fab fragments was compared in nude mice bearing grafts of a serially transplanted, CEA-producing, human colon carcinoma. The distribution of radiolabeled MAb and their fragments after intravenous injection was analyzed by direct measurement of radioactivity in tumor and normal organs, as well as by whole-body scanning and by autoradiography of tumor sections. Paired labeling experiments, in which 131I-labeled antibody or fragments and 125I-labeled control IgG are injected simultaneously, were undertaken to determine the relative tumor uptakes of each labeled protein. The tumor antibody uptake divided by that of control IgG defines the specificity index of localization. Tumor antibody uptakes (as compared with the whole mouse), ranging between 7 and 15, and specificity indices ranging between 3.4 and 6.8, were obtained with the four intact MAb at day 4-5 after injection. With F(ab')2 fragments of the four MAb, at day 3, the tumor antibody uptakes ranged between 12 and 24 and the specificity indices between 5.3 and 8.2. With the Fab fragments prepared from the two most promising MAb, the antibody uptakes reached values of 34 and 82 at day 2-3 and the specificity indices were as high as 12 and 19. The scanning results paralleled those obtained by direct measurement of radioactivity. With intact MAb, tumor grafts of 0.5-1 g gave very contrasted positive scans 3 d after injection. Using MAb fragments, tumors of smaller size were detectable earlier. The best results were obtained with Fab fragments of MAb 35, which gave clear detections of tumors weighing only 0.1 g as early as 48 h after injection. Autoradiographs of tumor sections from mice injected with 125I-labeled MAb demonstrated that the radioactivity was localized in the tumor tissues and not in the stromal connective tissue of mouse origin. The highest radioactivity concentration was localized in areas known to contain CEA such as the pseudolumen of glands and the apical side of carcinoma cells. The penetration of radioactivity in the central part of tumor nodules and the pseudolumen appeared to be increased with the use of MAb fragments.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Cesson, V., Stirnemann, K., Robert, B., Luescher, I., Filleron, T., Corradin, G., Mach, J.-P., Donda, A. (2006). Active Antiviral T-Lymphocyte Response Can Be Redirected against Tumor Cells by Antitumor Antibody x MHC/Viral Peptide Conjugates. Clin. Cancer Res. 12: 7422-7430 [Abstract] [Full Text]  
• Liu, G., Dou, S., Mardirossian, G., He, J., Zhang, S., Liu, X., Rusckowski, M., Hnatowich, D. J. (2006). Successful Radiotherapy of Tumor in Pretargeted Mice by 188Re-Radiolabeled Phosphorodiamidate Morpholino Oligomer, a Synthetic DNA Analogue.. Clin. Cancer Res. 12: 4958-4964 [Abstract] [Full Text]  
• Germain, C., Larbouret, C., Cesson, V., Donda, A., Held, W., Mach, J.-P., Pelegrin, A., Robert, B. (2005). MHC Class I-Related Chain A Conjugated to Antitumor Antibodies Can Sensitize Tumor Cells to Specific Lysis by Natural Killer Cells. Clin. Cancer Res. 11: 7516-7522 [Abstract] [Full Text]  
• Sharkey, R. M., Karacay, H., Richel, H., McBride, W. J., Rossi, E. A., Chang, K., Yeldell, D., Griffiths, G. L., Hansen, H. J., Goldenberg, D. M. (2003). Optimizing Bispecific Antibody Pretargeting for Use in Radioimmunotherapy. Clin. Cancer Res. 9: 3897s-3913s [Abstract] [Full Text]  
• Wu, A. M., Yazaki, P. J., Tsai, S.-w., Nguyen, K., Anderson, A.-L., McCarthy, D. W., Welch, M. J., Shively, J. E., Williams, L. E., Raubitschek, A. A., Wong, J. Y. C., Toyokuni, T., Phelps, M. E., Gambhir, S. S. (2000). High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc. Natl. Acad. Sci. USA 10.1073/pnas.150228297v1 [Abstract] [Full Text]  
• Firsov, D., Schild, L., Gautschi, I., Merillat, A.-M., Schneeberger, E., Rossier, B. C. (1996). Cell surface expression of the epithelial Na channel and a mutant causing Liddle syndrome: A quantitative approach. Proc. Natl. Acad. Sci. USA 93: 15370-15375 [Abstract] [Full Text]  
• Halpern, S. E., Dillman, R. O., Amox, D., Hagan, P. L., Burks, R., Dillman, J., Perdikakis, B., Merchant, B., Frincke, J. (1992). Detection of Occult Tumor Using Indium 111-Labeled Anticarcinoembryonic Antigen Antibodies. Arch Surg 127: 1094-1100 [Abstract]  
• Doerr, R. J., Abdel-Nabi, H., Merchant, B. (1990). Indium 111 ZCE-025 Immunoscintigraphy in Occult Recurrent Colorectal Cancer With Elevated Carcinoembryonic Antigen Level. Arch Surg 125: 226-229 [Abstract]  
• Duda, R. B., Beatty, J. D., Sheibani, K., Williams, L. E., Paxton, R. J., Beatty, B. G., Shively, J. E., Vlahos, W. G., Werner, J. L., Kemeny, M. M., Kokal, W. A., Riihimaki, D. U., Wagman, L. D., Terz, J. J. (1986). Imaging of Human Colorectal Adenocarcinoma With Indium-Labeled Anticarcinoembryonic Antigen Monoclonal Antibody. Arch Surg 121: 1315-1319 [Abstract]  
• Wu, A. M., Yazaki, P. J., Tsai, S.-w., Nguyen, K., Anderson, A.-L., McCarthy, D. W., Welch, M. J., Shively, J. E., Williams, L. E., Raubitschek, A. A., Wong, J. Y. C., Toyokuni, T., Phelps, M. E., Gambhir, S. S. (2000). High-resolution microPET imaging of carcinoembryonic antigen-positive xenografts by using a copper-64-labeled engineered antibody fragment. Proc. Natl. Acad. Sci. USA 97: 8495-8500 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS