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

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)

HIFU-mediated targeted drug delivery

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From Staruch et al., Int J Hyperthermia 2011

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

Computer Model:HIFU + LTSL

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TissueTemperature

Perfusion

Heat-Transfer Model

LTSL ReleaseLTSL Release

Pharmacokinetic Model

IntravascularSpace

Tissue

Mathematical Drug Delivery Model

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Drug delivery from LTSL in tumor(see also Gasselhuber et al., Int J Hyperthermia 2010)

Hyperthermia vs. HT+Ablation

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Temperature

Perfusion

Hyperthermia HT+Ablation

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Hyperthermia HT+Ablation

Drug Concentrations: HT + Ablation

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HIFU HIFU+Ablation

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