Immunotherapy with monoclonal antibodies has become an integral part of the treatment of B-cell non-Hodgkin’s lymphomas (NHL). Rituximab, an unlabelled monoclonal antibody to the CD20 antigen, was the first monoclonal antibody to be approved by the FDA for the treatment of cancer. This approval, in 1997, was based in part on the results of a pivotal clinical trial that treated 166 patients, with relapsed B-cell NHL, with rituximab 375 mg/m2 weekly × 4. The overall response rate (ORR) was 48% with 6% complete remission (CR) and a 13-month time-to-progression (TTP) . Rituximab is now widely used as a single agent for relapsed patients and combined with chemotherapy as initial treatment [2–4]. High response rates have also been demonstrated in previously untreated patients with low-grade NHL [5–10]. Immunotherapy has clearly been a major advance in the treatment of NHL; however, patients with advanced stage low-grade NHL are still considered ‘treatable but not usually curable’. New treatments are needed that build upon the success of rituximab immunotherapy.
Radioimmunotherapy (RIT) is a relatively new treatment for NHL that involves the linking of a high-energy, short-path length radionuclide to an antibody to form a radioimmunoconjugate (RIC). The goal of RIT is to use the targeting feature of a monoclonal antibody to focus radiation on the target cell population while sparing nearby normal tissues. The RIC kills tumour cells by the direct effects of the antibody, such as antibody-dependent cellular cytotoxicity, as well as the effects of ionising low-dose-rate radiation . The radionuclide can potentially be attached to any antibody. The choice of antibody depends on the antigenic profile of the tumour cell to be targeted. Ideal targets are those antigens that are expressed on tumour cells but not normal cells, so as to avoid toxicity to normal organs. Cell surface antigens that are not internalised or shed from the cell surface are preferred. Administration of the RIC is preceded by a dose of cold antibody in order to deplete normal blood B cells and block non-specific binding sites resulting in improved tumour to normal organ biodistribution. There are many different radionuclides that have been linked to antibodies for the treatment of cancer [12, 13]. Yttrium-90 (90Y) and iodine-131 (131I) are currently in common use and are commercially available (Table 10.1).
Table 10.1Characteristics of radionuclides currently used in radioimmunotherapy |Favorite Table|Download (.pdf) Table 10.1 Characteristics of radionuclides currently used in radioimmunotherapy
|Parameter ||131Iodine ||90Yttrium |
|Gamma emission ||Yes ||No |
|Beta emission ||Yes ||Yes |
|Beta emission path length ||0.8mm ||5mm |
|Theoretical half-life ||8 days ||2.4 days |
|Free radioisotope ||Thyroid/Stomach ||Bone |
|Administration ||Out-patient in most states ||Out-patient |
|Pre-treatment cold antibody required? ||Yes ||Yes |
|Useful for imaging and dosimetry? ||Yes ||No (111In required as a surrogate) |