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A spatiotemporal multi-scale computational model for FDG PET imaging at different stages of tumor growth and angiogenesis.

Authors
  • Kashkooli, Farshad Moradi1
  • Abazari, Mohammad Amin1
  • Soltani, M2, 3, 4, 5
  • Ghazani, Mehran Akbarpour1, 6
  • Rahmim, Arman7, 8, 9
  • 1 Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran. , (Iran)
  • 2 Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran. [email protected] , (Iran)
  • 3 Department of Electrical and Computer Engineering, Faculty of Engineering, School of Optometry and Vision Science, Faculty of Science, University of Waterloo, Waterloo, Canada. [email protected] , (Canada)
  • 4 Advanced Bioengineering Initiative Center, Multidisciplinary International Complex, K. N. Toosi University of Technology, Tehran, Iran. [email protected] , (Iran)
  • 5 Centre for Biotechnology and Bioengineering (CBB), University of Waterloo, Waterloo, ON, Canada. [email protected] , (Canada)
  • 6 Faculty of Mechanical Engineering, University of Tabriz, Tabriz, Iran. , (Iran)
  • 7 Department of Integrative Oncology, BC Cancer Research Institute, Vancouver, BC, Canada. , (Canada)
  • 8 Department of Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada. , (Canada)
  • 9 Department of Radiology, University of British Columbia, Vancouver, BC, Canada. , (Canada)
Type
Published Article
Journal
Scientific Reports
Publisher
Springer Nature
Publication Date
Jun 16, 2022
Volume
12
Issue
1
Pages
10062–10062
Identifiers
DOI: 10.1038/s41598-022-13345-4
PMID: 35710559
Source
Medline
Language
English
License
Unknown

Abstract

A deeper understanding of the tumor microenvironment (TME) and its role in metabolic activity at different stages of vascularized tumors can provide useful insights into cancer progression and better support clinical assessments. In this study, a robust and comprehensive multi-scale computational model for spatiotemporal transport of F-18 fluorodeoxyglucose (FDG) is developed to incorporate important aspects of the TME, spanning subcellular-, cellular-, and tissue-level scales. Our mathematical model includes biophysiological details, such as radiopharmaceutical transport within interstitial space via convection and diffusion mechanisms, radiopharmaceutical exchange between intracellular and extracellular matrices by glucose transporters, cellular uptake of radiopharmaceutical, as well as its intracellular phosphorylation by the enzyme. Further, to examine the effects of tumor size by varying microvascular densities (MVDs) on FDG dynamics, four different capillary networks are generated by angiogenesis modeling. Results demonstrate that as tumor grows, its MVD increases, and hence, the spatiotemporal distribution of total FDG uptake by tumor tissue changes towards a more homogenous distribution. In addition, spatiotemporal distributions in tumor with lower MVD have relatively smaller magnitudes, due to the lower diffusion rate of FDG as well as lower local intravenous FDG release. Since mean standardized uptake value (SUVmean) differs at various stages of microvascular networks with different tumor sizes, it may be meaningful to normalize the measured values by tumor size and the MVD prior to routine clinical reporting. Overall, the present framework has the potential for more accurate investigation of biological phenomena within TME towards personalized medicine. © 2022. The Author(s).

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