Effectiveness of radiolabelled antibodies for radio-immunotherapy in a colorectal xenograft model: a comparative study using the linear--quadratic formulation.
OBJECTIVE
To develop a model that relates the pattern of dose delivery during radio-immunotherapy to biological effect. This model was used to assess the efficacy of a range of antibodies labelled with 131I, 186Re and 90Y.


METHODS
Pharmacokinetic data were obtained by injecting tumour-bearing nude mice with radiolabelled antibody. The dose-rate in bone marrow and tumour was then given by a two-compartment model description of the pharmacokinetics combined with the radionuclide properties. Response characteristics 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 efficient clearance from blood. Matching the radionuclide with antibody pharmacokinetics and tumour type further increased this effect.


CONCLUSIONS
The model improves conceptual understanding of the relationship of parameters affecting therapy and makes it possible to optimize radio-immunotherapy by selecting the most effective antibody and radionuclide according to tumour biology.
Flynn
A A
AA
Department of Oncology, Royal Free and University College Medical School, London, UK. a.flynn@ucl.ac.uk
Pedley
R B
RB
Green
A J
AJ
Boxer
G M
GM
Boden
R
R
Dearling
J
J
Bhatia
J
J
Begent
R H
RH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001853:Bone Marrow / Q000528:radiation effects; D015179:Colorectal Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011879:Radiotherapy Dosage; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal