Carcinoembryonic antigen as a target for radioimmunotherapy of human medullary thyroid carcinoma: Antibody processing, targeting, and experimental therapy with I-131 and Y-90 labeled MAbs

The poor prognosis of patients with advanced medullary thyroid carcinoma (M TC) has prompted a search for new treatment modalities. In this report we e xplore the characteristics of carcinoembryonic antigen (CEA) as a target fo r radioimmunotherapy (RAIT) of MTC, with respect to antibody processing, ta rgeting, and experimental therapy. In vitro studies showed a high level of CEA expression on the cell surface of the MTC cell line TT. MAbs bound to t he cell were predominantly retained for several days, although there was al so a significant level of internalization and catabolism. Immunohistology o f frozen sections of tumor xenografts demonstrated that approximately half of the cells were darkly stained however, some cells expressed little or no CEA. In biodistribution studies in nude mice bearing IT ruiners, the mean percent injected dose per gram of tumor observed at three days post injecti on (time of maximum uptake) of I-125-MN-14 was 19.7%. When the MAb was labe led with Y-88, a residualizing label, a much higher accretion, 50.5%, was o bserved at the time of maximum uptake (7 days). Significant anti-tumor effe cts were seen at the maximum tolerated doses of I-131- and Y-90-MN-14, comp ared with relatively rapid tumor growth in untreated animals or those treat ed with the same dose of control MAbs. Importantly, it was observed that Y- 90-MN-14 yielded significantly improved therapeutic efficacy in comparison to I-131-MN-14, which may have important implications for design and conduc t of future clinical trials for the treatment of MTC.