Abstract
Significant improvements in tumor/nontumor ratio can be achieved by injections of nonlabeled anti-idiotypic monoclonal antibodies (MAbs) during radioimmunolocalization and radioimmunotherapy using MAbs to target experimental tumors. The in vivo effects of an anti-idiotypic MAb (αH7) against a radioiodinated, high affinity, low dissociation rate, monoclonal antiplacental alkaline phosphatase antibody (H7) was investigated. Following in vivo injection of the anti-idiotypic MAb, the radioactivity in experimental tumors was found to decrease only 25% while the reduction of corresponding radioactivity in nontumor tissues amounted to 65–85%, compared to the group receiving no anti-idiotypic MAbs. These results indicate that it is possible to partially clear the circulation and nontumor tissues from excess of radiolabeled idiotypic antibody, without significant decrease in specific tumor localization, increasing the tumor/ nontumor ratio three- to fourfold. Circulating nontumor targeting radiolabeled antibodies is one of the major limiting factors in radioimmunotherapy today. Injection of anti-idiotypic MAbs could selectively significantly reduce the radiation dose to radiosensitive tissues, i.e., bone marrow and intestine, thus improving efficiency in radioimmunoscintigraphy and radioimmunotherapy.
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Goldenberg, D., Deland, F., and Kim, E. (1978) Use of radiolabeled antibodies to carcinoembryonic antigen for detection and localization of diverse cancers by external photoscanning.N. Engl. J. Med. 298, 1384–1388.
Cheung, N.-K., Saarinen, U., Neely, J., Landmeir, B., Donovan, D., and Coccia, P. (1985) Monoclonal antibodies to a glycolipid antigen on human neuroblastoma cells.Cancer Res. 45, 2642–2649.
Scheinberg, D., Lovett, D., Divig, C., et al. (1991) A phase I trial of monoclonal antibody M195 in acute myelogenous leukemia: specific bone marrow targeting and internalization of radionuclide.J. Clin. Oncol. 9, 478–490.
Wheldon, T. E. and O’Donoghue, J. A. (1990) The radiobiology of targeted radiotherapy.Int. J. Biol. 58, 1.
Paganelli, G., Pervez, S., Siccardi, A., Rowlinson, G., Deleide, G., Chioleiro, F., et al. (1990) Intraperitoneal radiolocalisation of tumors pretargeted by biotinylated monoclonal antibodies.Int. J. Cancer 45, 1184–1189.
Paganelli, G., Malcovati, M., and Fazio, F. (1991) Monoclonal antibody pretargeting techniques for tumor localisation: the avidinbiotin system.Nucl. Med. Commun. 12, 211–234.
Norrgren, K., Strand, S., Nilsson, R., Lindgren, L., and Lilliehorn, P. (1991) Evaluation of extracorporeal immunoadsorption for reduction of the blood background in diagnostic and therapeutic application of radiolabeled antibodies.Antibody Immunoconj. Radiopharm. 4, 907–914.
Norrgren, K., Strand, S., Nilsson, R., Lindgren, L., and Sjögren, H. (1993) A general, extracorporeal immunoadsorption method to increase the tumor-to-normal tissue ratio in radioimmunoimaging and radioimmunotherapy.J. Nucl. Med. 34, 448–454.
Fjeld, J., Benestad, H., Stigbrand, T., and Nustad, K. (1988) In vivo evaluation of radiolabeled antibodies with antigen-coated polymer particles in diffusion chambers.J. Immunol. Methods 109, 1–7.
Sivalpenko, G., Kalofonos, H., Stewart, J., Hird, V., and Epenetos, A. (1992) Pharmacokinetics of radiolabeled murine monoclonal antibodies administered intravenously and intraperitoneally to patients with cancer for diagnosis and therapy.J. Pharm. Med. 2, 155–173.
Blumenthal, R., Sharkey, R., Kashi, R., and Goldenberg, D. (1989) Comparison of the therapeutic efficacy and host toxicity of two different131I-labeled antibodies and their fragments in the GW-39 colonic cancer xenograft model.Int. J. Cancer 44, 292–300.
Stigbrand, T., Hietala, S.-O., Johansson, B., Riklund, K., and Ekelund, L. (1989) Tumor radioimmunolocalization in nude mice by use of antiplacental alkaline phosphatase monoclonal antibodies.Tumor Biol. 10, 243–251.
Buchegger, F., Vacca, A., Carrel, S., Schreyer, M., and Mach, J.-P. (1988) Radioimmunotherapy of human colon carcinoma by131I-labeled monoclonal antibodies in a nude mice model.Int. J. Cancer 41, 412–427.
Sharkey, R., Blumenthal, R., and Goldenberg, D. (1990) Anti-antibody enhancement of tumor imaging, inCancer Imaging with Radiolabeled Antibodies (Goldenberg, D., ed.), Kluwer, Norwell, MA, pp. 433–455.
DeNardo, G., DeNardo, S., Kukis, D., Diril, H., Suey, C., and Meares, C. (1991) Strategies for enhancement of radioimmunotherapy.Nucl. Med. Biol. 18, 633–640.
Brown, B., Davis, G., Saltzgaber-Muller, J., Simon, P., Ho, M., and Shaw, P. (1987) Tumor-specific genetically engineered murine/human chimeric monoclonal antibody.Cancer Res. 47, 3577–3583.
Spar, I., Goodland, R., and Desidero, M. (1964) Immunological removal of circulating131I-labeled rabbit antibody to rat fibrinogen in normal and tumor-bearing rats.J. Nucl. Med. 5, 428–443.
Ullen, A., Nilsson, B., Riklund Åhlström, K., Makiya, R., and Stigbrand, T. (1995) In vivo and in vitro interactions between idiotypic and antiidiotypic monoclonal antibodies against placental alkaline phosphatase.J. Immunol. Methods, in press.
Goldenberg, D., Sharkey, R., and Ford, E. (1987) Anti-antibody enhancement of iodine-131 anti-CEA radioimmunodetection in experimental and clinical studies.J. Nucl. Med. 28, 1604–1610.
Sharkey, R., Boerman, O., Natale, A., Pawlyk, D., Monestier, M., Losman, M., and Goldenberg, D. (1992) Enhanced clearance of radiolabeled murine monoclonal antibody by a syngeneic anti-idiotype antibody in tumor bearing nude mice.Int. J. Cancer 51, 266–273.
Ullén, A., Sandström, P., Åhlström Riklund, K., Sundström, B., Nilsson, B., ärlestig, L., and Stigbrand, T. (1995) Use of anticytokeratin monoclonal antiidiotypic antibodies to improve tumor/non tumor ratio at experimental radioimmunolocalisation.Cancer Res., in press.
Goodwin, D., Meares, C., Diamanti, C., McCall, M., Corazon, L., Torti, F., et al. (1984) Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins.Eur. J. Nucl. Med. 9, 209–215.
Pedley, B., Dale, R., Boden, J., Begent, R., Keep, P., and Green, A. (1989) The effect of second antibody clearance on the distribution and dosimetry of radiolabelled anti-CEA antibody in a human colonic tumor xenograft model.Int. J. Cancer 43, 713–718.
Sharkey, R., Primus, J., and Goldenberg, D. (1984) Second antibody clearance of radiolabeled antibody in cancer radioimmunodetection.Proc. Natl. Acad. Sci. USA 81, 2843–2846.
Buchegger, F., Pèlegrin, A., Bischof-Delaloye, A., and Mach, J.-P. (1990) Iodine-131-labeled MAb F(ab) ′2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinomas grafted in nude mice.J. Nucl. Med. 31, 1035–1044.
Buchsbaum, D., Langmuir, V., and Wessels, B. (1993) Experimental radioimmunotherapy.Med. Phys. 20, 551–567.
Makiya, R. and Stigbrand, T. (1992) Placental alkaline phosphatase has a binding site for the human IgG internalization in Hep2 cells.Eur. J. Biochem. 205, 341–345.
Makiya, R. and Stigbrand, T. (1992) Placental alkaline phosphatase is related to human IgG internalization in Hep 2 cells.Biochem. Biophys. Res. Commun. 182, 624–630.
Makiya, R. and Stigbrand, T. (1992) Placental alkaline phosphatase, a GPI-anchored protein, is clustered in clathrin-coated vesicles.Biochem. Biophys. Res. Commun. 183, 803–808.
Riklund, K., Edbom, G., Makiya, R., Johansson, B., Gerdes, U., Hietala, S.-O., et al. (1991) Radioimmunoscintigraphy of gynecologic tumors with131I-labeled anti-PLAP monoclonal antibodies.Acta Radiol. 32, 375–380.
Millán, J. and Stigbrand, T. (1983) Antigenic determinants of human placental and testicular placental-like alkaline phosphatases as mapped by monoclonal antibodies.Eur. J. Biochem. 136, 1–7.
Sundström, B., Johansson, B., Hietala, S.-O., and Stigbrand, T. (1989) Diversity in immunoreactivity of tumor derived cytokeratin monoclonal antibodies.J. Histochem. Cytochem. 37, 1845–1854.
Greenwood, F., Hunter, W., and Glover, J. S. (1963) The preparation of131I-labeled human growth hormone of high specific radioactivity.J. Biochem. 89, 114–123.
Holmgren, P.-Å. and Stigbrand, T. (1976) Purification and partial characterization of two genetic variants of placental alkaline phosphatase.Biochem. Genetics 14, 777–789.
Löfås, S. and Johansson, B. (1990) A novel hydrogel matrix on gold surfaces in surface plasmon resonance sensors for fast and efficient covalent immobilization of ligands.J. Chem. Soc. Chem. Commun. 21, 1526–1528.
Fägerstam, L., Frostell, Å., Karlsson, R., Kullman, M., Larsson, A., Malmqvist, M., and Butt, H. (1990) Detection of antigen-antibody interactions by surface plasmon resonance.J. Mol. Recog. 3, 208–214.
Riklund, K., Makiya, R., Sundström, B., Thornell, L.-E., and Stigbrand, T. (1990) Experimental radioimmunotherapy of HeLa tumors in nude mice with131I-labeled monoclonal antibodies.Anticancer Res. 10, 379–384.
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Ullen, A., Riklund Åhlström, K., Makiya, R. et al. Syngeneic anti-idiotypic antibodies eliminate excess radiolabeled idiotypes at experimental radioimmunolocalization. Cell Biophysics 27, 31–45 (1995). https://doi.org/10.1007/BF02822525
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DOI: https://doi.org/10.1007/BF02822525