The U.S. Food and Drug Administration (FDA) approved two radioimmunotherapeutic agents, Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceuticals Corporation, San Diego, CA) in 2002 and Iodine-131 (131I) tositumomab (Bexxar; Corixa Corporation, South San Francisco, CA and GlaxoSmithKline, Philadelphia, PA) in 2003 for the treatment of relapsed or refractory low-grade, follicular, or transformed B-cell lymphoma. Yttrium-90 ibritumomab was approved in Europe in January 2004 (Zevalin; Schering AE, Berlin, Germany) and is at present the only radioimmunotherapy (RIT) available in Europe for this indication. Considered a scientific and clinical breakthrough, these radiolabelled monoclonal antibodies (MAbs) combined the targeted immune mechanisms of anti-CD20 immunotherapy with cytolytic ionising radiation to give patients durable remissions with minimal toxicity. Investigators reported response rates of 60–80% for patients with heavily pre-treated low-grade, follicular, and transformed lymphomas who were treated with 90Y ibritumomab tiuxetan and 131I tositumomab in phase I and II trials [1–8]. For responding patients, median disease-free survival was 6–14 months. With activity also observed in patients who were refractory to the anti-CD20 MAb, rituximab (Rituxan; Cellgene, Cambridge, MA), the clinical potential of these promising agents continues to expand [9, 10].
Though other radioimmunoconjugates have been developed, 90Y ibritumomab tiuxetan and 131I tositumomab remain the principle agents of RIT. Tositumomab is a murine, anti–CD20 antibody that targets the CD20 antigen on B lymphocytes. The antibody is directly chelated to 131I to create the radiolabelled MAb, 131I tositumomab. The formation of 90Y ibritumomab tiuxetan requires the linker protein, tiuxetan, to chelate 90Y to the murine, anti–CD20 immunoglobulin, ibritumomab.
There are no randomised studies to compare the efficacy of 131I tositumomab and 90Y ibritumomab tiuxetan, though an FDA-mandated trial is in progress. However, there are additional points to consider when selecting a radioimmunoconjugate for treatment. These agents have differences in terms of anti-tumour activity, radiation safety, treatment protocol, and toxicity that can impact clinical efficacy and patient’s quality of life. The differences are due to the inherent qualities of 90Y and 131I. Understanding how the radioisotope emission profile affects the radiolabelled MAb may provide guidance when selecting the best agent for each patient. This chapter will compare the advantages and disadvantages of 90Y and 131I and their respective radioimmunoconjugates. Factors that will be discussed include the properties of each radionuclide and radiation safety for patient, healthcare worker, and patient family, as well as therapy administration, treatment toxicities, and the impact that these factors have on a patient’s quality of life.
Radioisotopes vary in the type of radioactive emission, energy, path length, and half-life as well as biodistribution and stability. While a clearly superior radioisotope has not been identified, certain properties make radionuclides more attractive for immunoconjugation. Early RIT trials were conducted with 131I for several reasons: it was inexpensive, investigators were ...