A Model-Based Approach for Assessing the Efficacy of Radioimmunotherapy
Catherine
Lloyd
Bioengineering Institute, University of Auckland
Model Status
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
Model Structure
Radioimmunotherapy (RIT) is a treatment for cancer which combines radiation and immune therapy using monoclonal antibodies. RIT uses a radioactive material attached to specially designed antibodies to locate cancer within the body. Antibodies are defense proteins which are naturally produced by the body's immune system in order to fight infections caused by bacteria and other foreign pathogens. The antibodies used in RIT are monoclonal antibodies (MAbs) which are developed in the laboratory in order to recognise marker molecules on the surface of tumor cells. These antibodies are then modified to bind the radioactive metal Yttrium-90, which delivers high levels of local radiation to the tumour and subsequently destroys it.
The effectiveness of RIT is known to depend on at least six factors, including:
the totla absorbed dose and pattern of delivery;
radiosensitivity;
rate of repair of sublethal damage;
ongoing cancer proliferation during treatment;
tumour heterogeneity; and
tumour size.
Therefore no single parameter is a good indicator of how effective the RIT has been. Instead, several factors have to be simulataneously considered in order to get a more accurate characterisation of the biological effect.
The aim of this study by Flynn et al. was to develop a mathematical model that would relate the absorbed dose and its pattern of delivery to tumour response by incorporating information on each of the six influencing factors (see below). The mathemtical model was then used to optimise therapeutic efficacy in mice by matching the antibody and radionuclide characteristics while ensuring recoverable marrow toxicity.
The model has been described here in CellML (the raw CellML description of the Flynn et al. 2002 model can be downloaded in various formats as described in ).
The complete original paper reference is cited below:
A Model-Based Approach for the Optimization of Radioimmunotherapy through Antibody Design and Radionuclide Selection, Aiden A. Flynn, Alan J. Green, R. Barbara Pedley, Geoffrey M. Boxer, Jason Dearling, Rebecca Watson, Robert Boden, and Richard H. J. Begent, 2002,
Cancer
, 94, 1249-1257. (Full text (HTML) and PDF versions of the article are available to subscribers on the Cancer website.) PubMed ID: 11877753
reaction diagram
A schematic diagram of the three compartment model representing blood (B), viable tumour (V), and hypoxic tumour (H). Flow between compartments is governed by flow rate constants.
B
antibody concentration in the blood
$\frac{d B}{d \mathrm{time}}=-(\mathrm{lamda\_Bo}+\mathrm{lamda\_Vi})B$
V
antibody concentration in the viable tumour
$\frac{d V}{d \mathrm{time}}=\mathrm{lamda\_Vi}B-(\mathrm{lamda\_Vo}+\mathrm{lamda\_Ho})V$
H
antibody concentration in the hypoxic tumour
$\frac{d H}{d \mathrm{time}}=-(\mathrm{lamda\_Hi}V)+\mathrm{lamda\_Ho}H$
antibody_dose_rate
antibody dose-rate in the viable tumour
$\mathrm{RV}=\mathrm{A0}\mathrm{Eav}\mathrm{n\_beta}K(V\mathrm{phi}\mathrm{VV}+H\mathrm{phi}\mathrm{VH})\mathrm{RH}=\mathrm{A0}\mathrm{Eav}\mathrm{n\_beta}K(V\mathrm{phi}\mathrm{HV}+H\mathrm{phi}\mathrm{HH})$
S
surviving fraction
$S=e^{-(\mathrm{alpha}D)\mathrm{RE}}$
$\mathrm{total\_probability}=2.0P\int_{0}^{T} Re^{-\mathrm{mu}(T-\mathrm{time})}\,d \mathrm{time}\mathrm{probability\_of\_typeB\_damage}=2.0P^{2.0}\int_{0}^{\mathrm{time}} \int_{0}^{T} e^{-\mathrm{mu}(T-\mathrm{time})}\,d T\,d \mathrm{time}\mathrm{probability\_of\_typeB\_damage}=\mathrm{alpha}\int_{0}^{\mathrm{time}} R\,d \mathrm{time}$
immunology
tumour dynamics
antibody kinetics
radioimmunotherapy
Robert
Boden
Catherine
Lloyd
May
This is the CellML description of Flynn et al.'s 2002 model-based approach for assessing the efficacy of radioimmunotherapy.
Catherine Lloyd
A Model-Based Approach for the Optimization of Radioimmunotherapy through Antibody Design and Radionuclide Selection
94
1249
1257
Jason
Dearling
11877753
Geoffrey
Boxer
M
The University of Auckland, Bioengineering Institute
keyword
The University of Auckland
The Bioengineering Institute
Cancer
2002-02-15
Aiden
Flynn
A
2004-06-12
R
Pedley
Barbara
Flynn et al.'s 2002 model-based approach for assessing the efficacy of radioimmunotherapy.
Richard
Begent
H
J
c.lloyd@auckland.ac.nz
Rebecca
Watson
Alan
Green
J