1. 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 1 Dept. Pediatrics, Medical Univ. of South Carolina 2 Center for Interventional Oncology, National Cancer Institute

2. Disclosures none 2

3. 3 Low-Temperature Sensitive Liposomes (LTSL) Drug release (Doxorubicin) at hyperthermic temperatures Doxorubicin Release from LTSL (from Gasselhuber et al., Int J Hyperthermia 2010)

4. HIFU-mediated targeted drug delivery 4 From Staruch et al., Int J Hyperthermia 2011

5. 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

6. Computer Model: HIFU + LTSL 6 Tissue Temperature Perfusion Heat-Transfer Model LTSL Release Pharmacokinetic Model Intravascular Space Tissue

7. Mathematical Drug Delivery Model 7 Drug delivery from LTSL in tumor (see also Gasselhuber et al., Int J Hyperthermia 2010)

8. Hyperthermia vs. HT+Ablation 8 Temperature Perfusion Hyperthermia HT+Ablation

9. 9 Hyperthermia HT+Ablation

10. Drug Concentrations: HT + Ablation 10 HIFU HIFU+Ablation

11. 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

12. 12 Questions? ABLATION. MUSC.EDU Charleston, SC Funding: NIH R01CA118990, R21 CA135519