Effectiveness of radiolabelled antibodies for radio-immunotherapy in a colorectal xenograft model: a comparative study using the linear-quadratic formulation

Purpose: To develop a model that relates the pattern of dose delivery durin g radio-immunotherapy to biological effect. This model Was used to assess t he efficacy of a range of antibodies labelled with I-131, Re-186 and Y-90. Materials and methods: Pharmacokinetic data were obtained by injecting tumo ur-bearing nude mice with radiolabelled antibody. The dose-rate ill bone ma rrow and tumour was then given by a two-compartment model description of th e pharmacokinetics combined with the radionuclide properties. Response char acteristics of tumour and marrow were defined in terms of radiosensitivity, repair capacity and proliferation, and the biological effect was assessed using the linear-quadratic formulation. Results: Tumour-specific antibodies with intermediate molecular weight and clearance from the circulation delivered the most effective doses to tumour due to their rapid uptake and prolonged retention in tumour coupled with e fficient clearance from blood. Matching the radionuclide with antibody phar macokinetics and tumour type further increased this effect. Conclusions: The model improves conceptual understanding of the relationshi p of parameters affecting therapy and makes it possible to optimize radio-i mmunotherapy by selecting the most effective antibody and radionuclide acco rding to tumour biology.