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Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with (177)Lu- and (90)Y-BR96 mAbs.

Larsson, Erik LU ; Ljungberg, Michael LU ; Mårtensson, Linda; Nilsson, Rune LU ; Tennvall, Jan; Strand, Sven-Erik LU and Jönsson, Bo-Anders LU (2012) In Medical Physics 39(7). p.4434-4443
Abstract
Purpose:

Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study.



Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used... (More)
Purpose:

Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study.



Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with (90)Y- and (177)Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body.



Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for (177)Lu and 12.5 Gy for (90)Y.



Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose. (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
Medical Physics
volume
39
issue
7
pages
4434 - 4443
publisher
American Association of Physicists in Medicine
external identifiers
  • WOS:000306893000040
  • PMID:22830776
  • Scopus:84864254477
ISSN
0094-2405
DOI
10.1118/1.4730499
language
English
LU publication?
yes
id
36c5b969-afb5-4a59-a363-8a184cdf92ee (old id 2966637)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22830776?dopt=Abstract
date added to LUP
2012-08-10 08:10:33
date last changed
2016-10-13 04:27:49
@misc{36c5b969-afb5-4a59-a363-8a184cdf92ee,
  abstract     = {Purpose: <br/><br>
Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study.<br/><br>
<br/><br>
Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with (90)Y- and (177)Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body.<br/><br>
<br/><br>
Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for (177)Lu and 12.5 Gy for (90)Y.<br/><br>
<br/><br>
Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom weight, ranging from 225 g to 300 g, appeared to have no substantial effect for the estimated absorbed dose.},
  author       = {Larsson, Erik and Ljungberg, Michael and Mårtensson, Linda and Nilsson, Rune and Tennvall, Jan and Strand, Sven-Erik and Jönsson, Bo-Anders},
  issn         = {0094-2405},
  language     = {eng},
  number       = {7},
  pages        = {4434--4443},
  publisher    = {ARRAY(0x9969fe0)},
  series       = {Medical Physics},
  title        = {Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with (177)Lu- and (90)Y-BR96 mAbs.},
  url          = {http://dx.doi.org/10.1118/1.4730499},
  volume       = {39},
  year         = {2012},
}