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Parametric images of antibody pharmacokinetics based on serial quantitative whole-body imaging and blood sampling

Sjögreen Gleisner, Katarina LU ; Nickel, Mattias LU ; Lindén, Ola LU ; Erlandsson, Kjell; Wingårdh, Karin LU and Strand, Sven-Erik LU (2007) In Journal of Nuclear Medicine 48(8). p.1369-1378
Abstract
We present a method for pharmacokinetic modeling of distributions of In-111-labeled monoclonal antibodies (mAbs) on individual pixels of planar scintillation-camera images. Methods: The method is applied to 2 sets of clinical whole-body images, each consisting of 6 consecutive images acquired over a week. Quantification is performed on a pixel basis, yielding images in units of Bq/pixel. The images acquired on the different occasions are registered using a nonrigid method, and for each pixel location a time-activity curve is obtained for which kinetic modeling is performed. The In-111-mAb is assumed to be located in either the vascular or the extravascular space. The vascular content is assumed to follow the global blood kinetics as... (More)
We present a method for pharmacokinetic modeling of distributions of In-111-labeled monoclonal antibodies (mAbs) on individual pixels of planar scintillation-camera images. Methods: The method is applied to 2 sets of clinical whole-body images, each consisting of 6 consecutive images acquired over a week. Quantification is performed on a pixel basis, yielding images in units of Bq/pixel. The images acquired on the different occasions are registered using a nonrigid method, and for each pixel location a time-activity curve is obtained for which kinetic modeling is performed. The In-111-mAb is assumed to be located in either the vascular or the extravascular space. The vascular content is assumed to follow the global blood kinetics as determined from blood samples, together with a model parameter alpha that describes the fraction of the whole-body blood volume present in the particular pixel. The rate of change of the extravascular compartment is described by a linear 1-tissue-compartment model with 2 rate constants, K-1' and k(2), reflecting extravasation and washout, respectively. The model is optimized for each pixel position with regard to the values of the 3 parameters (alpha, K-1', and k(2)), resulting in 3 parametric images. From these, images of the cumulated activity in vascular and extravascular spaces are calculated, as is an image of the rate-constants ratio, which is closely related to the volume of distribution. Results: The resulting parametric images are analyzed in terms of the appearance of the time-activity curves at various locations. Results also include interpretation of the parametric images in their clinical context, and the location of regions that exhibit high extravasation and a low washout rate is compared with confirmed malignant sites. Conclusion: Parametric imaging allows the study and analysis of the spatial and temporal distributions of mAbs simultaneously. Parametric imaging enhances regions where the pharmacokinetics differ from the surrounding tissue and provides a tool to detect and locate unexpected kinetic behavior, which is sometimes characteristic of malignant tissue. For dosimetry in radionuclide therapy, parametric imaging offers a less biased means of analyzing serial mAb images than traditional region-of-interest-based analysis. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
parametric image, pharmacokinetic modeling, radioimmunoimaging, monoclonal antibody, rituximab
in
Journal of Nuclear Medicine
volume
48
issue
8
pages
1369 - 1378
publisher
Society of Nuclear Medicine
external identifiers
  • wos:000248584300035
  • scopus:34547822915
ISSN
0161-5505
DOI
10.2967/jnumed.107.039503
language
English
LU publication?
yes
id
82711546-4c70-4aab-9819-013668255142 (old id 691638)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17673426&dopt=Abstract
date added to LUP
2007-12-11 21:27:00
date last changed
2017-01-01 07:18:35
@article{82711546-4c70-4aab-9819-013668255142,
  abstract     = {We present a method for pharmacokinetic modeling of distributions of In-111-labeled monoclonal antibodies (mAbs) on individual pixels of planar scintillation-camera images. Methods: The method is applied to 2 sets of clinical whole-body images, each consisting of 6 consecutive images acquired over a week. Quantification is performed on a pixel basis, yielding images in units of Bq/pixel. The images acquired on the different occasions are registered using a nonrigid method, and for each pixel location a time-activity curve is obtained for which kinetic modeling is performed. The In-111-mAb is assumed to be located in either the vascular or the extravascular space. The vascular content is assumed to follow the global blood kinetics as determined from blood samples, together with a model parameter alpha that describes the fraction of the whole-body blood volume present in the particular pixel. The rate of change of the extravascular compartment is described by a linear 1-tissue-compartment model with 2 rate constants, K-1' and k(2), reflecting extravasation and washout, respectively. The model is optimized for each pixel position with regard to the values of the 3 parameters (alpha, K-1', and k(2)), resulting in 3 parametric images. From these, images of the cumulated activity in vascular and extravascular spaces are calculated, as is an image of the rate-constants ratio, which is closely related to the volume of distribution. Results: The resulting parametric images are analyzed in terms of the appearance of the time-activity curves at various locations. Results also include interpretation of the parametric images in their clinical context, and the location of regions that exhibit high extravasation and a low washout rate is compared with confirmed malignant sites. Conclusion: Parametric imaging allows the study and analysis of the spatial and temporal distributions of mAbs simultaneously. Parametric imaging enhances regions where the pharmacokinetics differ from the surrounding tissue and provides a tool to detect and locate unexpected kinetic behavior, which is sometimes characteristic of malignant tissue. For dosimetry in radionuclide therapy, parametric imaging offers a less biased means of analyzing serial mAb images than traditional region-of-interest-based analysis.},
  author       = {Sjögreen Gleisner, Katarina and Nickel, Mattias and Lindén, Ola and Erlandsson, Kjell and Wingårdh, Karin and Strand, Sven-Erik},
  issn         = {0161-5505},
  keyword      = {parametric image,pharmacokinetic modeling,radioimmunoimaging,monoclonal antibody,rituximab},
  language     = {eng},
  number       = {8},
  pages        = {1369--1378},
  publisher    = {Society of Nuclear Medicine},
  series       = {Journal of Nuclear Medicine},
  title        = {Parametric images of antibody pharmacokinetics based on serial quantitative whole-body imaging and blood sampling},
  url          = {http://dx.doi.org/10.2967/jnumed.107.039503},
  volume       = {48},
  year         = {2007},
}