Digital Twins for Personalized Healthcare: Application to Radiopharmaceutical Therapies
Abstract
Abstract
There is significant interest and value in utilizing digital twins (DTs) to extend healthcare from ‘one-size-fits-all’ to personalized therapies. Radiopharmaceutical therapies (RPTs), which represent very powerful developments in the battle against cancer, are no exceptions to this. In fact, theranostic digital twins (TDTs), which we elaborate in this work, present viable and feasible approaches to personalize RPTs. TDTs are computational representations of the human body that, unlike images, are operable; i.e. virtual trials can be conducted on them to propose optimal therapies for individual patients. TDTs can be built using physiologically based pharmacokinetic (PBPK) models. This work elaborates that TDTs can be developed in static, dynamic and interactive modes towards routine use in future clinical settings. TDTs will open a new area of theranostics research and development in terms of new radiopharmaceutical designs, synthesis and enabling of more optimal therapies.
1- George Sgouros, Lisa Bodei, Michael R McDevitt, and Jessie R Nedrow, "Radiopharmaceutical therapy in cancer: clinical advances and challenges." Nat Rev Drug Discov, Vol. 19 (No. 9), pp. 589-608, (2020).
2- Suliman Salih, Ajnas Alkatheeri, Wijdan Alomaim, and Aisyah Elliyanti, "Radiopharmaceutical treatments for cancer therapy, radionuclides characteristics, applications, and challenges." Molecules, Vol. 27 (No. 16), p. 5231, (2022).
3- Kilian E Salerno et al., "A Primer on Radiopharmaceutical Therapy." Int. J. Radiat. Oncol. Biol. Phys, Vol. 22 (No. In Press), (2022).
4- Cassandra Miller, Julie Rousseau, Caterina F Ramogida, Anna Celler, Arman Rahmim, and Carlos F Uribe, "Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs." Theranostics, Vol. 12 (No. 1), p. 232-59, (2022).
5- Julia Brosch-Lenz et al., "Role of Artificial Intelligence in Theranostics: Toward Routine Personalized Radiopharmaceutical Therapies." PET Clin, Vol. 16 (No. 4), pp. 627-41, (2021).
6- Tina Hernandez-Boussard et al., "Digital twins for predictive oncology will be a paradigm shift for precision cancer care." Nat Med Vol. 27 (No. 12), pp. 2065-66, (2021).
7- Stefan Mihai et al., "Digital twins: a survey on enabling technologies, challenges, trends and future prospects." IEEE Commun Surv & Tutor Vol 24 (No.4), pp.2255-91, (2022).
8- Maged N Kamel Boulos and Peng Zhang, "Digital twins: from personalised medicine to precision public health." J Pers Med, Vol. 11 (No. 8), p. 745, (2021).
9- Chengyue Wu et al., "Integrating mechanism-based modeling with biomedical imaging to build practical digital twins for clinical oncology." Biophys Rev, Vol. 3 (No. 2), p. 021304, (2022).
10- Genevieve Coorey et al., "The health digital twin to tackle cardiovascular disease—a review of an emerging interdisciplinary field." npj Digit Med, Vol. 5 (No. 1), pp. 1-12, (2022).
11- Reinhard Laubenbacher et al., "Building digital twins of the human immune system: toward a roadmap." npj Digit Med, Vol. 5 (No. 1), pp. 1-5, (2022).
12- Isabel Voigt, Hernan Inojosa, Anja Dillenseger, Rocco Haase, Katja Akgün, and Tjalf Ziemssen, "Digital twins for multiple sclerosis." Front Immunol, Vol. 12p. 669811, (2021).
13- Yingjie Chen, Ou Yang, Chaitanya Sampat, Pooja Bhalode, Rohit Ramachandran, and Marianthi Ierapetritou, "Digital twins in pharmaceutical and biopharmaceutical manufacturing: a literature review." Processes, Vol. 8 (No. 9), p. 1088, (2020).
14- Julia Brosch-Lenz, Carlos Uribe, Arman Rahmim, Babak Saboury, "Theranostic digital twins: An indispensable prerequisite for personalized cancer care." J Nucl Med, Accepted for Publication.
15- Arman Rahmim et al., "Theranostic Digital Twins for Personalized Radiopharmaceutical Therapies: Reimagining Theranostics via Computational Nuclear Oncology." Front Oncol, Accepted for Publication.
16- Riemer HJA Slart et al., "Long axial field of view PET scanners: a road map to implementation and new possibilities." Eur. J. Nucl. Med. Mol. Imaging, Vol. 48 (No. 13), pp. 4236-45, (2021).
17- Nicholas Navin and James Hicks, "Future medical applications of single-cell sequencing in cancer." Genome Med Vol. 3 (No. 5), pp. 1-12, (2011).
18- George M Grass and Patrick J Sinko, "Physiologically-based pharmacokinetic simulation modelling." Adv Drug Deliv Rev, Vol. 54 (No. 3), pp. 433-51, (2002).
19- P Zhao et al., "Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review." Clin Pharmacol Ther, Vol. 89 (No. 2), pp. 259-67, (2011).
20- Nastaran Shakourifar, Madjid Soltani, Farshad M Kashkooli, Julia Brosch-Lenz, Babak Saboury, and Arman Rahmim, "Effect of ligand amount and fraction of labeled peptides on internalized 177Lu-PSMA-I&T concentrations in tumors: Physiologically-based pharmacokinetic modeling." J Nucl Med, 63 (supplement 2) 2844, (2022).
21- Ali Fele Paranj, Julia Brosch-Lenz, Carlos Uribe, Arman Rahmim, and Babak Saboury, "Modular model architecture for radiopharmaceutical therapy planning: Physiologically-Based RadioPharmacoKinetics (PBRPK) implementation." J Nucl Med, 63 (supplement 2) 3197, (2022).
22- Deni Hardiansyah, Wei Guo, Ali Asgar Attarwala, Peter Kletting, Felix M Mottaghy, and Gerhard Glatting, "Treatment planning in PRRT based on simulated PET data and a PBPK model." Nuklearmedizin, Vol. 56 (No. 01), pp. 23-30, (2017).
23- François Bouzom, Kathryn Ball, Nathalie Perdaems, and Bernard Walther, "Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?" Biopharm. Drug Dispos, Vol. 33 (No. 2), pp. 55-71, (2012).
24- Mitchell Daneker, Zhen Zhang, George Em Karniadakis, and Lu Lu, "Systems Biology: Identifiability analysis and parameter identification via systems-biology informed neural networks." arXiv preprint arXiv:2202.01723, (2022).
25- Michela Del Prete et al., "Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial." Eur. J. Nucl. Med. Mol. Imaging, Vol. 46 (No. 3), pp. 728-42, (2019).
26- John Violet et al., "Dosimetry of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes." J Nucl Med, Vol. 60 (No. 4), pp. 517-23, (2019).
2- Suliman Salih, Ajnas Alkatheeri, Wijdan Alomaim, and Aisyah Elliyanti, "Radiopharmaceutical treatments for cancer therapy, radionuclides characteristics, applications, and challenges." Molecules, Vol. 27 (No. 16), p. 5231, (2022).
3- Kilian E Salerno et al., "A Primer on Radiopharmaceutical Therapy." Int. J. Radiat. Oncol. Biol. Phys, Vol. 22 (No. In Press), (2022).
4- Cassandra Miller, Julie Rousseau, Caterina F Ramogida, Anna Celler, Arman Rahmim, and Carlos F Uribe, "Implications of physics, chemistry and biology for dosimetry calculations using theranostic pairs." Theranostics, Vol. 12 (No. 1), p. 232-59, (2022).
5- Julia Brosch-Lenz et al., "Role of Artificial Intelligence in Theranostics: Toward Routine Personalized Radiopharmaceutical Therapies." PET Clin, Vol. 16 (No. 4), pp. 627-41, (2021).
6- Tina Hernandez-Boussard et al., "Digital twins for predictive oncology will be a paradigm shift for precision cancer care." Nat Med Vol. 27 (No. 12), pp. 2065-66, (2021).
7- Stefan Mihai et al., "Digital twins: a survey on enabling technologies, challenges, trends and future prospects." IEEE Commun Surv & Tutor Vol 24 (No.4), pp.2255-91, (2022).
8- Maged N Kamel Boulos and Peng Zhang, "Digital twins: from personalised medicine to precision public health." J Pers Med, Vol. 11 (No. 8), p. 745, (2021).
9- Chengyue Wu et al., "Integrating mechanism-based modeling with biomedical imaging to build practical digital twins for clinical oncology." Biophys Rev, Vol. 3 (No. 2), p. 021304, (2022).
10- Genevieve Coorey et al., "The health digital twin to tackle cardiovascular disease—a review of an emerging interdisciplinary field." npj Digit Med, Vol. 5 (No. 1), pp. 1-12, (2022).
11- Reinhard Laubenbacher et al., "Building digital twins of the human immune system: toward a roadmap." npj Digit Med, Vol. 5 (No. 1), pp. 1-5, (2022).
12- Isabel Voigt, Hernan Inojosa, Anja Dillenseger, Rocco Haase, Katja Akgün, and Tjalf Ziemssen, "Digital twins for multiple sclerosis." Front Immunol, Vol. 12p. 669811, (2021).
13- Yingjie Chen, Ou Yang, Chaitanya Sampat, Pooja Bhalode, Rohit Ramachandran, and Marianthi Ierapetritou, "Digital twins in pharmaceutical and biopharmaceutical manufacturing: a literature review." Processes, Vol. 8 (No. 9), p. 1088, (2020).
14- Julia Brosch-Lenz, Carlos Uribe, Arman Rahmim, Babak Saboury, "Theranostic digital twins: An indispensable prerequisite for personalized cancer care." J Nucl Med, Accepted for Publication.
15- Arman Rahmim et al., "Theranostic Digital Twins for Personalized Radiopharmaceutical Therapies: Reimagining Theranostics via Computational Nuclear Oncology." Front Oncol, Accepted for Publication.
16- Riemer HJA Slart et al., "Long axial field of view PET scanners: a road map to implementation and new possibilities." Eur. J. Nucl. Med. Mol. Imaging, Vol. 48 (No. 13), pp. 4236-45, (2021).
17- Nicholas Navin and James Hicks, "Future medical applications of single-cell sequencing in cancer." Genome Med Vol. 3 (No. 5), pp. 1-12, (2011).
18- George M Grass and Patrick J Sinko, "Physiologically-based pharmacokinetic simulation modelling." Adv Drug Deliv Rev, Vol. 54 (No. 3), pp. 433-51, (2002).
19- P Zhao et al., "Applications of physiologically based pharmacokinetic (PBPK) modeling and simulation during regulatory review." Clin Pharmacol Ther, Vol. 89 (No. 2), pp. 259-67, (2011).
20- Nastaran Shakourifar, Madjid Soltani, Farshad M Kashkooli, Julia Brosch-Lenz, Babak Saboury, and Arman Rahmim, "Effect of ligand amount and fraction of labeled peptides on internalized 177Lu-PSMA-I&T concentrations in tumors: Physiologically-based pharmacokinetic modeling." J Nucl Med, 63 (supplement 2) 2844, (2022).
21- Ali Fele Paranj, Julia Brosch-Lenz, Carlos Uribe, Arman Rahmim, and Babak Saboury, "Modular model architecture for radiopharmaceutical therapy planning: Physiologically-Based RadioPharmacoKinetics (PBRPK) implementation." J Nucl Med, 63 (supplement 2) 3197, (2022).
22- Deni Hardiansyah, Wei Guo, Ali Asgar Attarwala, Peter Kletting, Felix M Mottaghy, and Gerhard Glatting, "Treatment planning in PRRT based on simulated PET data and a PBPK model." Nuklearmedizin, Vol. 56 (No. 01), pp. 23-30, (2017).
23- François Bouzom, Kathryn Ball, Nathalie Perdaems, and Bernard Walther, "Physiologically based pharmacokinetic (PBPK) modelling tools: how to fit with our needs?" Biopharm. Drug Dispos, Vol. 33 (No. 2), pp. 55-71, (2012).
24- Mitchell Daneker, Zhen Zhang, George Em Karniadakis, and Lu Lu, "Systems Biology: Identifiability analysis and parameter identification via systems-biology informed neural networks." arXiv preprint arXiv:2202.01723, (2022).
25- Michela Del Prete et al., "Personalized 177Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: initial results from the P-PRRT trial." Eur. J. Nucl. Med. Mol. Imaging, Vol. 46 (No. 3), pp. 728-42, (2019).
26- John Violet et al., "Dosimetry of 177Lu-PSMA-617 in metastatic castration-resistant prostate cancer: correlations between pretherapeutic imaging and whole-body tumor dosimetry with treatment outcomes." J Nucl Med, Vol. 60 (No. 4), pp. 517-23, (2019).
| Files | ||
| Issue | Vol 10 No 1 (2023) | |
| Section | Editorial | |
| DOI | https://doi.org/10.18502/fbt.v10i1.11505 | |
| Keywords | ||
| Digital Twins Radiopharmaceutical Therapies Theranostics Personalized therapy PBPK models | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Abdollahi H, Rahmim A. Digital Twins for Personalized Healthcare: Application to Radiopharmaceutical Therapies. Frontiers Biomed Technol. 2022;10(1):1-5.
