This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sharkey, R. M. Articles by Goldenberg, D. M. Search for Related Content PubMed PubMed Citation Articles by Sharkey, R. M. Articles by Goldenberg, D. M.

Radioimmunotherapy of the GW-39 Human Colonic Tumor Xenograft with ¹³¹I-labeled Murine Monoclonal Antibody to Carcinoembryonic Antigen¹

Center for Molecular Medicine and Immunology [R. M. S., M. J. P., F. J. P., D. M. G.] and New Jersey Medical School [E. A. A., F. J. P., D. M. G.], University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103, and Department of Diagnostic Imaging [J. A. S.], Temple University Hospital, Philadelphia, Pennsylvania 19140

We have investigated the therapeutic efficacy of a single injection of ¹³¹I-labeled murine mouse monoclonal antibody (NP-4) against carcinoembryonic antigen using the human colonic tumor xenograft, GW-39, grown in the cheek pouches of adult hamsters. Therapeutic efficacy was dependent on the dose of radioactivity, the specificity of the antibody for the tumor, and the size of the tumor when the radioantibody was administered. A dose of 1 mCi of ¹³¹I-labeled NP-4 given 1 day after tumor transplantation completely inhibited the growth of 6 of 11 tumors over a 12-week period, and histological evidence indicated that viable tumor was absent in the tissue remaining at the injection site. Lower doses (0.5 mCi) of ¹³¹I-labeled NP-4 inhibited tumor growth over 90% in comparison to untreated animals, but the tumors eventually resumed growth. Delaying the administration of radioantibody for 4 or 7 days after tumor transplantation significantly reduced the therapeutic efficacy. Although the same dose of ¹³¹I-labeled irrelevant immunoglobulin G also inhibited tumor growth, ¹³¹I-labeled NP-4 was generally 2–3 times more effective in reducing tumor growth than was the control IgG. There was a 13% loss in body weight within 7 days after treatment with 1 mCi, but all the animals regained their weight by day 14, indicating that the level of radioactivity was tolerated well. Dosimetric calculations predicted that over 14 days a dose of nearly 2400 rads was delivered to the tumors with ¹³¹I-labeled NP-4. These results confirm our previous studies that ¹³¹I-labeled antibody can effectively inhibit tumor growth, but suggest that radioantibody therapy is most effectively administered when there is a low tumor burden.

¹ These studies were supported in part by NIH OIA Grant CA 39841 (D.M.G.), NIH Grant CA 37218 (F.J.P.), and University of Medicine and Dentistry of New Jersey Foundation Grant 4-87 (E.A.A.).

² To whom requests for reprints should be addressed, at Center for Molecular Medicine and Immunology, 1 Bruce St., Newark, NJ 07103.

Received 5/ 8/87. Revised 8/ 6/87. Accepted 8/10/87.

This article has been cited by other articles:

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Perspectives on Cancer Therapy with Radiolabeled Monoclonal Antibodies J. Nucl. Med., January 1, 2005; 46(1_suppl): 115S - 127S. [Abstract] [Full Text] [PDF]

				F. G. van Schaijk, E. Oosterwijk, A. C. Soede, W. J. G. Oyen, W. J. McBride, G. L. Griffiths, D. M. Goldenberg, F. H. M. Corstens, and O. C. Boerman Pretargeting with Labeled Bivalent Peptides Allowing the Use of Four Radionuclides: 111In, 131I, 99mTc, and 188Re Clin. Cancer Res., September 1, 2003; 9(10): 3880S - 3885. [Abstract] [Full Text] [PDF]