Syngeneic anti-idiotypic antibodies eliminate excess radiolabeled idiotypes at experimental radioimmunolocalization
- 24 Downloads
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.
Index EntriesMonoclonal antibodies anti-idiotypic antibodies biospecific interaction analyses placental alkaline phosphatase radioimmunolocalization radioimmunotherapy
Unable to display preview. Download preview PDF.
- 4.Wheldon, T. E. and O’Donoghue, J. A. (1990) The radiobiology of targeted radiotherapy.Int. J. Biol. 58, 1.Google Scholar
- 7.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.Google Scholar
- 10.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.Google Scholar
- 14.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.Google Scholar
- 15.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.Google Scholar
- 18.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.Google Scholar
- 21.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.Google Scholar
- 25.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.PubMedGoogle Scholar
- 33.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.Google Scholar