ABSTRACT
The use of monoclonal antibody (mAb) in routine clinical practice is now well established and has led to significant improvements in outcome for patients with haematological malignancies as well as in a wide range of other malignancies, including breast and bowel cancer.1,2 Although the single-agent activity of most mAb has been modest, when used in combination with other anti-tumour therapies, an additive or synergistic effect has been seen.3 The combination of mAb and multi-agent chemotherapy in a number of different histologies of non-Hodgkin’s lymphoma (NHL) has led not only to highly impressive increases in response rates, but also to improved relapsefree survival and even overall survival.3,4
Radioimmunotherapy (RIT) is the administration of therapeutic radioisotopes targeted to tumour through chemical conjugation to mAb or mAb-derived constructs. Monoclonal antibodies were initially regarded simply as direct carriers for the radioisotope that delivers systemically targeted cytotoxic radiation to areas of disease with relative sparing of normal tissue. It is, however, becoming clear that during RIT for lymphoma, the mAb effector mechanisms may also play an important additional role in killing tumour cells. The nature of RIT determines that its efficacy depends on a number of factors, including the properties of the targeted antigen (specificity, density, availability, shedding and heterogeneity of expression), the tumour (volume, degree of vascularization, blood flow and permeability), the mAb (specificity, immunoreactivity, stability and affinity) and the
properties of the chosen radioisotope (emission characteristics, half-life and availability).5
