title: The effect of tumour size on drug transport and uptake in 3-D tumour models reconstructed from magnetic resonance images.
abstract: Drug transport and its uptake by tumour cells are strongly dependent on tumour properties, which vary in different types of solid tumours. By simulating the key physical and biochemical processes, a numerical study has been carried out to investigate the transport of anti-cancer drugs in 3-D tumour models of different sizes. The therapeutic efficacy for each tumour is evaluated by using a pharmacodynamics model based on the predicted intracellular drug concentration. Simulation results demonstrate that interstitial fluid pressure and interstitial fluid loss vary non-linearly with tumour size. Transvascular drug exchange, driven by the concentration gradient of unbound drug between blood and interstitial fluid, is more efficient in small tumours, owing to the low spatial-mean interstitial fluid pressure and dense microvasculature. However, this has a detrimental effect on therapeutic efficacy over longer periods as a result of enhanced reverse diffusion of drug to the blood circulation after the cessation of drug infusion, causing more rapid loss of drug in small tumours.
authors.affiliation: Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Zhan
authors.affiliation: Department of Radiology, Imperial College Healthcare NHS Trust, St Mary's Hospital, London, United Kingdom.
authors.forename: Wladyslaw
authors.initials: W
authors.lastname: Gedroyc
authors.affiliation: Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, United Kingdom.
authors.forename: Xiao Yun
authors.identifier: http://orcid.org/0000-0002-8267-621X
authors.initials: XY
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007091:Image Processing, Computer-Assisted; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D016062:Porosity; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D004317:Doxorubicin