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Development and evaluation of a pharmacokinetic model for prediction of radioimmunotherapy based on pretherapy data.

Nickel, Mattias LU ; Strand, Sven-Erik LU ; Lindén, Ola LU ; Wingårdh, Karin LU ; Tennvall, Jan LU and Sjögreen Gleisner, Katarina LU (2009) In Cancer Biotherapy & Radiopharmaceuticals 24(1). p.111-121
Abstract
The aim of this work was to develop a pharmacokinetic model for the analysis of the pharmacokinetics of (111)Inlabeled monoclonal antibodies (mAbs) in B-cell lymphoma patients and to evaluate the model's ability to predict a subsequent radioimmunotherapy by (90)Y-labeled mAbs. Data from quantified scintillation camera images and blood samples were used to fit a compartment model. The modeling included two steps: 1) a two-compartment model describing the total-body kinetics for the estimation of a set of global parameters and 2) a multicompartment model for estimating the model parameters for organs. In both steps, a correction for radiochemical impurity in the form of (111)In-DTPA (diethylene triamine pentaacetic acid) was included. The... (More)
The aim of this work was to develop a pharmacokinetic model for the analysis of the pharmacokinetics of (111)Inlabeled monoclonal antibodies (mAbs) in B-cell lymphoma patients and to evaluate the model's ability to predict a subsequent radioimmunotherapy by (90)Y-labeled mAbs. Data from quantified scintillation camera images and blood samples were used to fit a compartment model. The modeling included two steps: 1) a two-compartment model describing the total-body kinetics for the estimation of a set of global parameters and 2) a multicompartment model for estimating the model parameters for organs. In both steps, a correction for radiochemical impurity in the form of (111)In-DTPA (diethylene triamine pentaacetic acid) was included. The model was found to describe all patient data with good accuracy. From the model, the time-activity data of all organs could be separated into extravascular and vascular components, where the estimates of the regional vascular volumes were found to be in close agreement with literature data. A significant improvement of the model fit to total-body activity data was obtained by correcting for radiochemical impurity. The therapy kinetics area under the curves (AUCs) predicted from pretherapy data were in good agreement with the measured therapy AUCs. The good correlation between the model estimates and measured data, the accurate prediction of the therapy kinetics, and the good estimates of regional vascular volumes demonstrates the reliability of the model. These findings also indicate that the model can be useful for individual optimization of the amount of activity to be administered with respect to patient dosimetry. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Biotherapy & Radiopharmaceuticals
volume
24
issue
1
pages
111 - 121
publisher
Mary Ann Liebert, Inc.
external identifiers
  • wos:000263898300015
  • pmid:19243253
  • scopus:60849133912
ISSN
1557-8852
DOI
10.1089/cbr.2008.0530
language
English
LU publication?
yes
id
2fa3aa9f-2833-4792-914d-5aa621b0543a (old id 1302184)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19243253?dopt=Abstract
date added to LUP
2009-03-09 13:28:13
date last changed
2017-01-01 07:53:20
@article{2fa3aa9f-2833-4792-914d-5aa621b0543a,
  abstract     = {The aim of this work was to develop a pharmacokinetic model for the analysis of the pharmacokinetics of (111)Inlabeled monoclonal antibodies (mAbs) in B-cell lymphoma patients and to evaluate the model's ability to predict a subsequent radioimmunotherapy by (90)Y-labeled mAbs. Data from quantified scintillation camera images and blood samples were used to fit a compartment model. The modeling included two steps: 1) a two-compartment model describing the total-body kinetics for the estimation of a set of global parameters and 2) a multicompartment model for estimating the model parameters for organs. In both steps, a correction for radiochemical impurity in the form of (111)In-DTPA (diethylene triamine pentaacetic acid) was included. The model was found to describe all patient data with good accuracy. From the model, the time-activity data of all organs could be separated into extravascular and vascular components, where the estimates of the regional vascular volumes were found to be in close agreement with literature data. A significant improvement of the model fit to total-body activity data was obtained by correcting for radiochemical impurity. The therapy kinetics area under the curves (AUCs) predicted from pretherapy data were in good agreement with the measured therapy AUCs. The good correlation between the model estimates and measured data, the accurate prediction of the therapy kinetics, and the good estimates of regional vascular volumes demonstrates the reliability of the model. These findings also indicate that the model can be useful for individual optimization of the amount of activity to be administered with respect to patient dosimetry.},
  author       = {Nickel, Mattias and Strand, Sven-Erik and Lindén, Ola and Wingårdh, Karin and Tennvall, Jan and Sjögreen Gleisner, Katarina},
  issn         = {1557-8852},
  language     = {eng},
  number       = {1},
  pages        = {111--121},
  publisher    = {Mary Ann Liebert, Inc.},
  series       = {Cancer Biotherapy & Radiopharmaceuticals},
  title        = {Development and evaluation of a pharmacokinetic model for prediction of radioimmunotherapy based on pretherapy data.},
  url          = {http://dx.doi.org/10.1089/cbr.2008.0530},
  volume       = {24},
  year         = {2009},
}