TY - GEN
T1 - Study of the most important physiologic parameter using GSA with sobol method and a PBPK model for individualization of peptide-receptor radionuclide therapy
AU - Luthfy, Dzikrillah H.A.M.
AU - Misrawati,
AU - Ittaqa, Ai Nurainun
AU - Riana, Ade
AU - Hardiansyah, Deni
N1 - Funding Information:
This work was supported by Departement of Medical Physics and Biophysics, Universitas Indonesia (Hibah PUTI Prosiding 2020, Grant Number: NKB-986/UN2.RST/HKP.05.00/2020) for this research and publication. The authors thank the supervisor who has provided guidance and support for the completion of this study.
Publisher Copyright:
© 2021 American Institute of Physics Inc.. All rights reserved.
PY - 2021/3/2
Y1 - 2021/3/2
N2 - In this study, we identified the most important physiologic parameters determining the variability of the organ at risk and tumor absorbed doses (ADs) in Peptide-receptor radionuclide therapy (PRRT). Therefore, a global sensitivity analysis (GSA) with Sobol method and a physiologically-based pharmacokinetic (PBPK) model were used. A whole-body PBPK model that has been developed for treatment planning in PRRT therapy for meningioma and neuroendocrine patients was used. The physiologic parameters of interest for the GSA analysis were the parameters that have been previously estimated from the biokinetic data and were reported in the literature, i.e. the organ receptor densities Rd, organ flows f, organ release rates, and peptide binding rate. GSA with Sobol method was chosen based on its accuracy for sensitivity studies. A widely used GSA MATLAB-based toolbox (https://www.safetoolbox.info/) and an in-house program based on MATLAB software (version R2018b) were used for the analysis. The sampling method with a log-normal distribution was used to avoid any negative values of the sampled parameters. The main effects Si and total effects STi were calculated and analyzed using the GSA program and the PBPK model to identify the importance of each model parameter i for the individualization of the ADs in PRRT. To warrant the convergence of the calculated Si and STi, various numbers of model simulations up to 15000 samples were used. The inter-individual variability of tumor ADs (coefficients of variation CV up to 97.05%) was higher than that in the organ at risk (e.g. kidneys CV around 31.59%). Receptor density was identified as the most important parameters determined the ADs of tumors, e.g. [RdTU2]: Si = 0.856, STi = 0.951. The same results was found for the organ at risk where the receptor density had the highest main effect and total effect values, e.g. [RdK]: Si = 0.802, STi = 0.963. We have shown the first implementation of the GSA with the Sobol method to identify the most important parameters for the individualization of the calculated ADs in PRRT. Our results suggested an accurate measurement of the receptor densities for an accurate determination of the tumor and organ at risk ADs.
AB - In this study, we identified the most important physiologic parameters determining the variability of the organ at risk and tumor absorbed doses (ADs) in Peptide-receptor radionuclide therapy (PRRT). Therefore, a global sensitivity analysis (GSA) with Sobol method and a physiologically-based pharmacokinetic (PBPK) model were used. A whole-body PBPK model that has been developed for treatment planning in PRRT therapy for meningioma and neuroendocrine patients was used. The physiologic parameters of interest for the GSA analysis were the parameters that have been previously estimated from the biokinetic data and were reported in the literature, i.e. the organ receptor densities Rd, organ flows f, organ release rates, and peptide binding rate. GSA with Sobol method was chosen based on its accuracy for sensitivity studies. A widely used GSA MATLAB-based toolbox (https://www.safetoolbox.info/) and an in-house program based on MATLAB software (version R2018b) were used for the analysis. The sampling method with a log-normal distribution was used to avoid any negative values of the sampled parameters. The main effects Si and total effects STi were calculated and analyzed using the GSA program and the PBPK model to identify the importance of each model parameter i for the individualization of the ADs in PRRT. To warrant the convergence of the calculated Si and STi, various numbers of model simulations up to 15000 samples were used. The inter-individual variability of tumor ADs (coefficients of variation CV up to 97.05%) was higher than that in the organ at risk (e.g. kidneys CV around 31.59%). Receptor density was identified as the most important parameters determined the ADs of tumors, e.g. [RdTU2]: Si = 0.856, STi = 0.951. The same results was found for the organ at risk where the receptor density had the highest main effect and total effect values, e.g. [RdK]: Si = 0.802, STi = 0.963. We have shown the first implementation of the GSA with the Sobol method to identify the most important parameters for the individualization of the calculated ADs in PRRT. Our results suggested an accurate measurement of the receptor densities for an accurate determination of the tumor and organ at risk ADs.
UR - http://www.scopus.com/inward/record.url?scp=85102273865&partnerID=8YFLogxK
U2 - 10.1063/5.0037546
DO - 10.1063/5.0037546
M3 - Conference contribution
AN - SCOPUS:85102273865
T3 - AIP Conference Proceedings
BT - 9th National Physics Seminar 2020
A2 - Nasbey, Hadi
A2 - Fahdiran, Riser
A2 - Indrasari, Widyaningrum
A2 - Budi, Esmar
A2 - Bakri, Fauzi
A2 - Prayitno, Teguh Budi
A2 - Muliyati, Dewi
PB - American Institute of Physics Inc.
T2 - 9th National Physics Seminar 2020
Y2 - 20 June 2020
ER -