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Radiolocalization of Xenografted Human Malignant Melanoma by a Monoclonal Antibody (9.2.27) to a Melanoma-associated Antigen in Nude Mice¹

Biological Therapeutics Branch, Biological Response Modifiers Program, Division of Cancer Treatment, National Cancer Institute, NIH, Frederick Cancer Research Facility, Frederick, Maryland 21701 [A. C. M., R. K. O.]; Program Resources, Inc., NCI-Frederick Cancer Research Facility, Frederick, Maryland 20701 [K. M. H.]; and Norsk Hydros Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo 3, Norway [O. F.]

A murine monoclonal antibody (9.2.27), directed to a M_r 250,000 glycoprotein-chondroitan sulfate proteoglycan complex, was radiolabeled with ¹²⁵I and assessed for radiolocalization in tumor and normal tissues of normal and tumor-bearing nude mice. The ¹²⁵I-9.2.27 localized in vivo preferentially in M_r 250,000 antigen-expressing human melanomas (FMX-Met, SESX) but not in low antigen-expressing tumors (LOX-L) xenografted in nude mice. The imaging index of tumor cells was positively correlated with the antigen density of the various melanoma cell lines as measured by flow cytometry. The nonspecific immunoglobulin RPC-5 of the same IgG2a subclass as 9.2.27 did not specifically localize to xenografts of melanoma. The total amount of ¹²⁵I-9.2.27 accumulated in the tumor was directly correlated with tumor size. However, the specific radioactivity (cpm/g) in smaller tumors was higher than that in larger tumors.

Nonspecific uptake and circulating antibody levels differed between normals and tumor-bearers. The organs of the reticuloendothelial system of normal mice accumulated more labeled antibody than did those of tumor bearers, and conversely, tumor bearers had higher levels of circulating labeled antibody in the blood than normals. The circulating labeled antibody in tumor bearers was still monomeric but had no detectable antigen-binding capacity.

¹ This project has been funded at least in part with Federal funds from the Department of Health and Human Services, under Contract NO1-CO-23910 with Program Resources, Inc.

² Present address: NeoRx Corporation, 410 W. Harrison, Seattle, WA 98119. To whom requests for reprints should be addressed.

Received 12/23/83. Revised 5/14/85. Accepted 5/16/85.

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