A PBPK model for PRRT with [177Lu]Lu-DOTA-TATE : Comparison of model implementations in SAAM II and MATLAB/SimBiology
(2024) In Physica Medica 119.- Abstract
Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software. Methods: A combined PBPK model for [68Ga]Ga-DOTA-TATE and... (More)
Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [177Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software. Methods: A combined PBPK model for [68Ga]Ga-DOTA-TATE and [177Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared. Results: The PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations. Conclusion: The proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology.
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- author
- Vasić, Valentina ; Gustafsson, Johan LU ; Nowshahr, Elham Yousefzadeh ; Stenvall, Anna LU ; Beer, Ambros J. ; Gleisner, Katarina Sjögreen LU and Glatting, Gerhard
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Comparison of model implementations, Peptide receptor radionuclide therapy, Physiologically based pharmacokinetic model
- in
- Physica Medica
- volume
- 119
- article number
- 103299
- publisher
- ISTITUTI EDITORIALI E POLGRAFICI INTERNAZIONALI
- external identifiers
-
- pmid:38367588
- scopus:85185576943
- ISSN
- 1120-1797
- DOI
- 10.1016/j.ejmp.2024.103299
- language
- English
- LU publication?
- yes
- id
- 059f169f-fa5b-4d3f-81b5-e6d4046bcf0a
- date added to LUP
- 2024-03-26 15:39:06
- date last changed
- 2024-04-23 19:34:44
@article{059f169f-fa5b-4d3f-81b5-e6d4046bcf0a,
abstract = {{<p>Physiologically based pharmacokinetic (PBPK) models offer the ability to simulate and predict the biodistribution of radiopharmaceuticals and have the potential to enable individualised treatment planning in molecular radiotherapy. The objective of this study was to develop and implement a whole-body compartmental PBPK model for peptide receptor radionuclide therapy (PRRT) with [<sup>177</sup>Lu]Lu-DOTA-TATE in SimBiology to allow for more complex analyses. The correctness of the model implementation was ensured by comparing its outputs, such as the time-integrated activity (TIA), with those of a PBPK model implemented in SAAM II software. Methods: A combined PBPK model for [<sup>68</sup>Ga]Ga-DOTA-TATE and [<sup>177</sup>Lu]Lu-DOTA-TATE was developed and implemented in both SAAM II and SimBiology. A retrospective analysis of 12 patients with metastatic neuroendocrine tumours (NETs) was conducted. First, time-activity curves (TACs) and TIAs from the two software were calculated and compared for identical parameter values. Second, pharmacokinetic parameters were fitted to activity concentrations, analysed and compared. Results: The PBPK model implemented in SimBiology produced TIA results comparable to those generated by the model implemented in SAAM II, with a relative deviation of less than 0.5% when using the same input parameters. The relative deviation of the fitted TIAs was less than 5% when model parameter values were fitted to the measured activity concentrations. Conclusion: The proposed PBPK model implemented in SimBiology can be used for dosimetry in radioligand therapy and TIA prediction. Its outputs are similar to those generated by the PBPK model implemented in SAAM II, confirming the correctness of the model implementation in SimBiology.</p>}},
author = {{Vasić, Valentina and Gustafsson, Johan and Nowshahr, Elham Yousefzadeh and Stenvall, Anna and Beer, Ambros J. and Gleisner, Katarina Sjögreen and Glatting, Gerhard}},
issn = {{1120-1797}},
keywords = {{Comparison of model implementations; Peptide receptor radionuclide therapy; Physiologically based pharmacokinetic model}},
language = {{eng}},
publisher = {{ISTITUTI EDITORIALI E POLGRAFICI INTERNAZIONALI}},
series = {{Physica Medica}},
title = {{A PBPK model for PRRT with [<sup>177</sup>Lu]Lu-DOTA-TATE : Comparison of model implementations in SAAM II and MATLAB/SimBiology}},
url = {{http://dx.doi.org/10.1016/j.ejmp.2024.103299}},
doi = {{10.1016/j.ejmp.2024.103299}},
volume = {{119}},
year = {{2024}},
}