Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: a pre-clinical study in a genetic model of pancreatic cancer

AbstractPurpose: The lack of effective treatment options for pancreatic cancer has led to a 5-year survival rate of just 8%. Here, we evaluate the ability to enhance targeted drug deliveryusing mild hyperthermiain combination with the systemic administrationof a low-temperature sensitive liposomal formulation of doxorubicin(LTSL-Dox) using a relevant model for pancreas cancer.Materials and methods: Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre). LTSL-Dox or free doxorubicin(Dox) was administered via a tail vein catheter. A clinical magnetic resonance-guided high intensity focussed ultrasound (MR-HIFU) system was used to plan treatment, apply the HIFU-induce hyperthermiaand monitor therapy. Post-therapy, total Dox concentration in tumour tissue was determined by HPLC and confirmed with fluorescence microscopy.Results: Localized hyperthermiawas successfully applied and monitored with a clinical MR-HIFU sy...