MR-guided HIFU enhanced targeted drug delivery for treatment of pancreas cancer: a pre-clinical study

Project Name: MR-guided HIFU enhanced targeted drug delivery for treatment of pancreas cancer: a pre-clinical study
Status: Complete
Primary Site: University of Washington
Sponsor Organization: Focused Ultrasound Foundation
Funded Date: Mar 09, 2012
Funding Period: Mar 09, 2012 -
Funding Program: Liver/Pancreas Program
Category: Pre-Clinical
Amount Awarded: $164,995.00

Abstract

Pancreatic cancer accounts for 5% of cancer deaths in the United States and is the fourth leading cause of cancer mortality. Current treatment options are of limited benefit with a 5-year survival rate following diagnosis of less than 5%. The application of HIFU for tumor therapy has been gaining momentum due to advances in imaging technology such as MR thermometry that permits real0time monitoring of HIFU treatment effects. Although ablation of pancreatic tumors has been performed, ablation carries significant risks such as pancreatitis and bowel perforation. The application of HIFU to enhance targeted deliver of chemotherapeutic agents has been reported in pre-clinical studies. However, mechanisms are still poorly understood and few survival studies have been performed. A new temperature sensitive liposomal drug delivery system for doxorubicin that is released by hypothermic temperatures (39.5-42C) has been developed (ThermoDox (R), Clesion, Columbia, MD). ThermoDox has the potential for being activated by MR-guided HIFU with MR thermometry used to control the temperature of the target tissue to optimize release and delivery of the drug. In addition to thermal release of the drug, HIFU has the additional potential benefit for enhancing penetration of drug after it has been released due to the mechanical effects of HIFU (radiation force and microstreaming). The overall aim of this pilot study is to investigate whether HIFU-induced hyperthermia in conjunction with systemically administered ThermoDox will result in higher tissue concentration and penetration of doxorubicin compared to tissue that is treated with HIFU to induce hyperthermia in conjunction with systemic administration of a non-thermosensitive liposomal formulation of doxorubicin (Doxil).

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