The goal of radioimmunotherapy (RIT) is to deliver cytotoxic radiation from therapeutic radioisotopes to tumours using mAbs (similar to a guided missile) that bind to those cells expressing the target antigen (Hainsworth, 2000; Cheson, 2001). The success of RIT depends on several factors, including the choice of the target antigens, antibody molecules (guided missiles) and therapeutic radioisotopes (Juweid, 2002), e.g. ideally the target antigen should be tumour specific and expressed only on tumour cells with no level of expression on normal cells. In practice, most of the target antigens recognized by antibodies are tumour-associated antigens that are also present in lower numbers on the surface of normal cells. To minimize exposure of such normal cells to the radioisotope, a relatively high dose of unlabelled antibody is given to the patients, either before or with the administration of various radiolabelled antibodies. The two most common isotopes that are used in RIT are iodine-131 (131I) and yttrium-90 (90Y) (Dillman, 2002; Juweid, 2002). The advantage of radioimmunotherapy over unconjugated antibodies in cancer therapy is that the former has a longer path, which allows further deeper penetration and killing of tumour cells (both antigen positive and negative) without direct binding of antibody to such tumours.
Ibritumomab tiuxetan (Zevalin) is the first RIT agent that was approved for the treatment of cancer in February 2002 (Dillman, 2002). Zevalin is a 90Y-labelled anti-CD20 antibody (IDEC Pharmaceuticals, USA) which has been shown to produce a 74% response rate in Rituxan-refractory NHL patients. To determine the relative efficacy of
Zevalin (90Y-labelled anti-CD20 antibody) to unconjugated anti-CD20 antibody (Rituxan) in the treatment of patients with NHL, 143 NHL patients were randomized into two groups, in a phase 3 clinical trial. The overall response rate in patients treated with Zevalin and Rituxan was 80% and 56% respectively. As explained above, the advantage of RIT over unconjugated mAb is that the former penetrates deeper into the tumour mass and can also kill antigen-negative tumours in a crossfire effect. Therefore, patients who are not responsive to, or relapse after chemotherapy or treatment with unconju-gated antibodies, may be suitable candidates for RIT approaches (Dillman, 2002; Foran, 2002; Juweid, 2002).
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