Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125. Gynecol Oncol

The application of intraperitoneal (i.p.) radioimmunotherapy to treat i.p. tumor loci has been limited by bone marrow toxicity secondary to circulating radiolabeled antibodies. The generation of novel genetically engi-neered monoclonal antibodies, which can achieve high tumor uptake and rapid blood clearance, should en-hance the therapeutic index of i.p. radioimmunotherapy. In this regard, a novel humanized anti-TAG-72 mono-clonal antibody with a deleted CH2 region (HuCC49CH2) has been described, which localized well to subcutaneous xenograft tumors and had a rapid plasma clearance. The aim of this study was to examine the characteristics of this radiolabeled reagent when administered through the i.p. route in mice bearing i.p. tu-mor (LS174T). The CH2 molecule and intact humanized CC49 (HuCC49) monoclonal antibody were con-jugated to PA-DOTA and radiolabeled with 177Lu. Both molecules retained high-affinity binding to TAG-72 positive LS174T tumor cells in vitro. The radiolabeled CH2 molecule had a modest decrease in tumor lo-calization, as compared to the intact molecule when administered i.p. to tumor-bearing mice and a dramat-ically shorter plasma disappearance T1/2 at 2.7 hours compared to 61.2 hours for the intact antibody. The radiolabeled CH2 molecule thus had very high tumor:blood ratios. Using an 131I-labeled system, the max-imum tolerated dose of CH2 was>3 that of intact HuCC49. Autoradiography of tumors showed low ra