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Distribution of Radiolabeled Human and Mouse Monoclonal IgM Antibodies in Murine Models

Veterans Administration Medical Center, San Diego
University of California, San Diego
Hybritech, Inc., La Jolla, California

Correspondence: For reprints contact: Samuel E. Halpern, MD, Nuclear Medicine Service (115), VA Medical Center, 3350 La Jolla Village Dr., San Diego, CA 92161.

ABSTRACT

The distribution and kinetics of six human and one murine monoclonal IgM antibodies (MoAb) were studied in BALB/c mice. Labeling was with ¹¹¹In, ⁷⁵Se, and ¹²⁵I. The monomers and pentamers of certain MoAbs were studied. Human distribution studies were also performed. The serum containing [¹¹¹In]MoAb was obtained from one of the patients 24 hr after administration and injected into mice which were then killed and assayed for ¹¹¹In distribution. In general, the [⁷⁵Se] and [¹¹¹In]MoAbs had distribution and kinetic patterns that were similar while the ¹²⁵I-labeled MoAbs dehalogenated after 4 hr. Monomers and pentamers had highly similar distributions suggesting that the distribution of IgMs may be based on factors other than molecular size. The murine IgM showed a somewhat different distribution in mice than did human IgMs. Serum from the patient containing [¹¹¹In]MoAb had a distribution in mice similar to that of the patient with high liver and gastrointestinal uptake. The human imaging indicates that it is possible to target tumor with human IgM MoAbs, but significant problems remain in regard to their clinical use.