Radiopharmaceutical transport in solid tumors via a 3-dimensional image-based spatiotemporal model.

Autor: Piranfar A; Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran., Moradi Kashkooli F; Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran., Zhan W; School of Engineering, King's College, University of Aberdeen, Aberdeen, AB24 3UE, UK., Bhandari A; Biofluids Research Lab, Department of Mechanical Engineering, Indian Institute of Technology (Indian School of Mines), Dhanbad, 826004, India., Saboury B; Department of Computational Nuclear Oncology, Institute of Nuclear Medicine, Bethesda, MD, USA.; Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada., Rahmim A; Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada.; Departments of Radiology and Physics, University of British Columbia, Vancouver, BC, Canada., Soltani M; Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran. msoltani@uwaterloo.ca.; Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada. msoltani@uwaterloo.ca.; Department of Electrical and Computer Engineering, University of Waterloo, Waterloo, ON, Canada. msoltani@uwaterloo.ca.; Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON, Canada. msoltani@uwaterloo.ca.
Jazyk: angličtina
Zdroj: NPJ systems biology and applications [NPJ Syst Biol Appl] 2024 Apr 12; Vol. 10 (1), pp. 39. Date of Electronic Publication: 2024 Apr 12.
DOI: 10.1038/s41540-024-00362-4
Abstrakt: Lutetium-177 prostate-specific membrane antigen ( 177 Lu-PSMA)-targeted radiopharmaceutical therapy is a clinically approved treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). Even though common practice reluctantly follows "one size fits all" approach, medical community believes there is significant room for deeper understanding and personalization of radiopharmaceutical therapies. To pursue this aim, we present a 3-dimensional spatiotemporal radiopharmaceutical delivery model based on clinical imaging data to simulate pharmacokinetic of 177 Lu-PSMA within the prostate tumors. The model includes interstitial flow, radiopharmaceutical transport in tissues, receptor cycles, association/dissociation with ligands, synthesis of PSMA receptors, receptor recycling, internalization of radiopharmaceuticals, and degradation of receptors and drugs. The model was studied for a range of values for injection amount (100-1000 nmol), receptor density (10-500 nmol•l -1 ), and recycling rate of receptors (10 -4 to 10 -1  min -1 ). Furthermore, injection type, different convection-diffusion-reaction mechanisms, characteristic time scales, and length scales are discussed. The study found that increasing receptor density, ligand amount, and labeled ligands improved radiopharmaceutical uptake in the tumor. A high receptor recycling rate (0.1 min -1 ) increased radiopharmaceutical concentration by promoting repeated binding to tumor cell receptors. Continuous infusion results in higher radiopharmaceutical concentrations within tumors compared to bolus administration. These insights are crucial for advancing targeted therapy for prostate cancer by understanding the mechanism of radiopharmaceutical distribution in tumors. Furthermore, measures of characteristic length and advection time scale were computed. The presented spatiotemporal tumor transport model can analyze different physiological parameters affecting 177 Lu-PSMA delivery.
(© 2024. The Author(s).)
Databáze: MEDLINE
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