Ferritin concentration and 131I-antiferritin tumor localization in an experimental hepatoma

Polyclonal 131I-labeled rabbit anti-rat ferritin was shown to specifically localize in the H4IIe rat hepatoma model. Tumor targeting was shown to be maximal in primary tumors or metastatic lesions less than 1 gram. Radiolabeled antiferritin tumor targeting decreased with increasing tumor size. In this study, ferritin levels were measured in H4IIe tumors grown both in vitro and in vivo. In vitro tumor cells synthesized and secreted ferritin into the medium as measured by radioimmunoassay, and confirmed by the incorporation of 14C-leucine into ferritin synthesis. The concentration of ferritin in the tumor cells as measured by radioimmunoassay remained relatively constant over this same time period. In vivo tumor ferritin levels in whole tumor extracts were highest in small tumors (less than 1 gram) and decreased as the tumors became larger. Serum ferritin levels of tumor-bearing animals paralleled the level in the tumors themselves. The elevated serum ferritin levels in animals with small tumors did not inhibit tumor targeting with radiolabeled antiferritin antibody. These findings are a foundation for understanding the selective tumor targeting of tumor associated proteins by radiolabeled antibodies, which includes factors such as tumor size, vascularity, antigen content, and circulating antigen.