Autoradiographic Evaluation of Monoclonal Antibodies Access to Melanoma-Associated Antigens in Melanoma Xenografts

Abstract

Autoradiography of nude mice bearing human malignant melanoma xenografts was performed to characterize the distribution pattern of radioiodinated anti-melanoma monoclonal antibodies (MoAb) and fragments in macroscopic tumor nodules. Non-uniformity of radioactivity distribution was seen in all MoAb-xenograft combinations. The predominant patterns were marked deposition of radioactivity either in the periphery of nodules or in sharply delimited intra-tumoral foci. These patterns were generated by limitations in the accessibility of melanoma tissue rather than gross necrosis or heterogeneity of antigen expression. Computer-aided densitometry of autoradiograms was used to elaborate the difference of accumulation in intra-tumoral hot spots versus cold areas. It was found that increasing uniformity was achieved by increasing the dose of MoAb (i.e., intact IgG) injected, whereas a reduction in the size of MoAb (IgG greater than F(ab')2 greater than Fab) showed no such effect.