Klein J L, Kopher K A, Rostock R A
Int J Radiat Oncol Biol Phys. 1986 Jan;12(1):137-40. doi: 10.1016/0360-3016(86)90428-1.
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.
多克隆131I标记的兔抗大鼠铁蛋白在H4IIe大鼠肝癌模型中显示出特异性定位。在小于1克的原发性肿瘤或转移灶中，肿瘤靶向性最高。随着肿瘤大小的增加，放射性标记的抗铁蛋白肿瘤靶向性降低。在本研究中，测量了体外和体内生长的H4IIe肿瘤中的铁蛋白水平。通过放射免疫测定法测量，体外肿瘤细胞合成并分泌铁蛋白到培养基中，并通过将14C-亮氨酸掺入铁蛋白合成中得到证实。在同一时间段内，通过放射免疫测定法测量的肿瘤细胞中铁蛋白浓度保持相对恒定。在整个肿瘤提取物中，体内肿瘤铁蛋白水平在小肿瘤（小于1克）中最高，并随着肿瘤变大而降低。荷瘤动物的血清铁蛋白水平与肿瘤本身的水平平行。小肿瘤动物中升高的血清铁蛋白水平并未抑制放射性标记的抗铁蛋白抗体的肿瘤靶向性。这些发现是理解放射性标记抗体对肿瘤相关蛋白的选择性肿瘤靶向性的基础，其中包括肿瘤大小、血管生成、抗原含量和循环抗原等因素。
