Radiolabelled monoclonal antibodies in tumour imaging and therapy: out of fashion?

Abstract

The initial enthusiasm for the development of diagnostic and therapeutic studies involving the use of monoclonal antibodies was replaced by scepticism as hopes remained unfulfilled. Against this background one needs to ask whether immunoscintigraphy (IS) serves clinical needs effectively and whether radioimmunotherapy (RIT) has a future. The current review considers these questions by reference to relevant studies. Taking colorectal cancer as an example, an appraisal is offered of the ability of IS to detect disease at an early stage and thereby to reduce mortality, and of the influence of the results of IS on patient management. It is concluded that in a limited number of cases of colorectal cancer and other solid tumors, IS will allow surgery to be performed at a stage where cure is still possible because of its ability to detect early recurrence. Turning to RIT, the results of studies in respect of various tumour types are reviewed, with due attention to reported toxicity. As regards colorectal cancer, no consistent therapeutic effects have been achieved, and myelotoxicity is typically the dose-limiting factor. Thus many questions remain to be answered, regarding antigens to be targeted, fractionation schedule, the use of "humanised" antibodies, choice of radionuclide and the use of intact immunoglobulins or fragments. These questions are considered. Overall it is concluded that the most promising application of RIT is as adjuvant therapy in patients with minimal residual disease, and a controlled multicentre trial is recommended. The development of more potent radio-immunoconjugates for therapeutic and ultimately diagnostic purposes will contribute to the improvement and development of IS by increasing its potential to influence prognosis.