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HIFU mediated drug delivery: Vascular shutdown facilitates drug depot effect
Gasselhuber A.1, Appanaboyina S. 1, Dreher M.R.2, Wood B.J.2, Haemmerich D.1
1Dept. Pediatrics, Medical Univ. of South Carolina2Center for Interventional Oncology, National Cancer Institute
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Disclosures
none
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Low-Temperature Sensitive Liposomes (LTSL)
Drug release (Doxorubicin) at hyperthermic temperatures
Doxorubicin Release from LTSL(from Gasselhuber et al., Int J Hyperthermia 2010)
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HIFU-mediated targeted drug delivery
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From Staruch et al., Int J Hyperthermia 2011
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Computer Simulation of HIFU+LTSL drug delivery• Heat transfer model• Drug Delivery Model
Two heating scenarios: 7 min hyperthermia (42 ºC) 7 min hyperthermia + brief ablation pulse
(to shut down blood flow)
Study Goal
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Computer Model:HIFU + LTSL
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TissueTemperature
Perfusion
Heat-Transfer Model
LTSL ReleaseLTSL Release
Pharmacokinetic Model
IntravascularSpace
Tissue
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Mathematical Drug Delivery Model
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Drug delivery from LTSL in tumor(see also Gasselhuber et al., Int J Hyperthermia 2010)
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Hyperthermia vs. HT+Ablation
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Temperature
Perfusion
Hyperthermia HT+Ablation
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Hyperthermia HT+Ablation
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Drug Concentrations: HT + Ablation
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HIFU HIFU+Ablation
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Elimination of blood flow by brief high-temperature heating pulse considerably increases tissue drug uptake Depot Effect Other blood flow reducing methods
(embolization) would have similar effect
Summary
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Questions?
ABLATION. MUSC.EDUCharleston, SC
Funding: NIH R01CA118990, R21 CA135519