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Immunoreactivity and Biodistribution of Indium-111-Labeled Monoclonal Antibody to a Human High Molecular Weight-Melanoma Associated Antigen

Departments of Radiology (Nuclear Medicine) and Surgery, College of Physicians and Surgeons, Columbia University, New York; Medical Department, Brookhaven National Laboratories, Upton; and Department of Microbiology and Immunology, New York Medical College, Valhalla, New York

Correspondence: For reprints contact: Rashid A. Fawwaz, MD, PhD, Div. of Nuclear Medicine, Columbia University College of Physicians and Surgeons, 630 West 168th St., New York, NY 10032.

ABSTRACT

The anti-human, high molecular weight-melanoma associated antigen (HMW-MAA) MoAb 225.28S was chelated with ¹¹¹ln and then tested for its in vitro reactivity with cultured human melanoma cells and for its biodistribution in human melanoma bearing nude mice. In vitro studies showed that the radiolabeled antibody reacted specifically with cultured melanoma cells. However, binding of DTPA to the monoclonal antibody reduced its titer with cultured melanoma cells from 1:1024 to 1:512. Further labeling of the DTPA-antibody conjugate with ¹¹¹ln caused an additional reduction of its titer to 1:128. Injection of the radiolabeled monoclonal antibody into nude mice resulted in the accumulation of significantly (p < 0.001) higher radioactivity in melanoma tissue than in nude mice injected with either [¹¹¹ln]chloride or ¹¹¹ln-labeled antibody to human acid phosphatase. The specificity of the distribution of the radiolabeled antibody in nude mice also was indicated by its poor localization in lesions other than melanoma (e.g., human prostate carcinoma and chronic abscess). The localization of antibody in liver and kidney was also high, although lower than that achieved in tumor. These results indicate that ¹¹¹ln-labeled monoclonal antibodies to human tumor associated antigens may be useful for localizing malignant lesions. However, there is a need to improve labeling and/or purification of antibody in order to decrease renal and hepatic activity.