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 Heiner, J. P. Articles by Cheung, N.-K. V. Search for Related Content PubMed PubMed Citation Articles by Heiner, J. P. Articles by Cheung, N.-K. V.

Localization of G_D2-specific Monoclonal Antibody 3F8 in Human Osteosarcoma¹

Departments of Orthopaedics [J. P. H., J. M.], Radiology [F. M.], and Pediatrics [S. K., W. H. S-M., N-K. V. C.], Rainbow Babies and Childrens Hospital and University Hospitals of Cleveland, Case Western Reserve University, Cleveland, Ohio 44106, and Hershey Medical Center, Hershey, Pennsylvania [J. N.]

3F8 is a murine IgG3 monoclonai antibody specific for the antigen disialoganglioside G_D2. Immunofluorescence staining showed strong binding of 3F8 to 15 of 17 human osteosarcomas, including primary and metastatic tumors. The targeting potentials of the native monoclonal antibody (3F8) and the F(ab')₂ fragment (p-3F8) were tested in BALB/c athymic nude mice xenografted with human osteosarcomas. After radiolabeling with iodine using the chloramine T method, both 3F8 and p-3F8 retained immunoreactivities. The irrelevant IgG3 antibody TIB114 and its F(ab')₂ fragment were used as negative controls. A Ewing's sarcoma xenograft, which was low in G_D2 antigen, was also studied for comparison. Mice were sacrified 1 day and 4 days after i.v. antibody injection. 3F8 and p-3F8 showed preferential accumulation in osteosarcoma over normal tissues with tumor:nontumor ratios of 2.7–58:1 and 1.4–82:1, respectively, on Day 1. These ratios improved to 10–163:1 and 6.0–75:1 on Day 4. The intact antibody 3F8 showed selective tumor uptake with a much higher percentage of injected dose per g than the fragment p-3F8 and exhibited a longer tissue half-life than p-3F8. These data indicate that anti-G_D2 monoclonal antibodies may be useful for imaging and targeted therapy of human osteogenic sarcoma. The F(ab')₂ fragment has the advantage of achieving favorable tumor:nontumor ratios sooner after antibody injection while the intact antibody shows better retention by tumor tissues.

¹ Supported by Grant ACS-CDA-4-85 from the American Cancer Society and in part by USPHS Grant CA-39320 from the National Cancer Institute and grants from the Ireland Cancer Center, Cleveland, OH.

² Present address: University of Wisconsin Hospitals and Clinics, Madison, WI 53792.

³ Present address: Hershey Medical Center, Hershey, PA.

⁴ To whom requests for reprints should be addressed, at Memorial Sloan Kettering Cancer Center, 1275 York Ave. New York, NY 10021.

Received 3/30/87. Revised 6/24/87. Accepted 7/22/87.

This article has been cited by other articles:

				N. Marina, M. Gebhardt, L. Teot, and R. Gorlick Biology and Therapeutic Advances for Pediatric Osteosarcoma Oncologist, July 1, 2004; 9(4): 422 - 441. [Abstract] [Full Text] [PDF]

				I. Y. Cheung and N.-K. V. Cheung Quantitation of Marrow Disease in Neuroblastoma by Real-Time Reverse Transcription-PCR Clin. Cancer Res., June 1, 2001; 7(6): 1698 - 1705. [Abstract] [Full Text] [PDF]

				S. Modak, K. Kramer, S. H. Gultekin, H. F. Guo, and N.-K. V. Cheung Monoclonal Antibody 8H9 Targets a Novel Cell Surface Antigen Expressed by a Wide Spectrum of Human Solid Tumors Cancer Res., May 1, 2001; 61(10): 4048 - 4054. [Abstract] [Full Text]