Radioimmunotherapy of Human Colonic Cancer Xenografts with ⁹⁰Y-labeled Monoclonal Antibodies to Carcinoembryonic Antigen¹

Monoclonal antibodies (MAbs) to carcinoembryonic antigen (CEA) or α-fetoprotein (AFP) were conjugated with diethylenetriaminepentaacetic acid and radiolabeled with ⁹⁰Y at a specific activity of 4.0–6.0 mCi/mg. Approximately 50% of the radiolabeled anti-CEA antibody (⁹⁰Y-labeled NP-2) bound to an immunoadsorbent containing CEA while analysis by high performance liquid chromatography revealed that 95–98% of the ⁹⁰Y was associated with immunoglobulin. Less than 5% of the ⁹⁰Y dissociated from either MAb after incubation in plasma for 48 h at 37°C. After injection into nude mice, 98% of the circulating radioactivity remained associated with antibody and no loss of immunoreactivity was observed at 3 days. To evaluate ⁹⁰Y-labeled NP-2 as a therapeutic agent, varied doses (10–100 µCi) were administered as a single i.v. injection into groups of nude mice bearing s.c. implants (0.3–0.4 g) of a CEA-producing human colonic cancer xenograft, GW-39. At the 10-µCi dose, no inhibition of tumor growth was observed. After 28 days, tumor growth was inhibited by as much as 77% in mice treated with 50 µCi of ⁹⁰Y-labeled NP-2 as compared to tumor growth in control animals given ⁹⁰Y-labeled anti-AFP. Doses higher than 50 µCi (75 and 100 µCi) were toxic to most of the animals, killing them within 2–3 weeks after administration. Marked suppression of circulating leukocytes was observed with 20 and 50 µCi by 1–2 weeks postinjection, but they returned to normal levels 3–4 weeks later. These studies show that treatment with ⁹⁰Y-labeled MAbs against CEA can produce significant antitumor effects. However, toxicity to the bone marrow may limit the therapeutic efficacy of systemically administered ⁹⁰Y-labeled MAbs.