Hyperthermia-enhanced targeted drug delivery using magnetic resonance-guided focussed ultrasound: a pre-clinical study in a genetic model of pancreatic cancer. International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group Farr, N. n., Wang, Y. N., D'Andrea, S. n., Starr, F. n., Partanen, A. n., Gravelle, K. M., McCune, J. S., Risler, L. J., Whang, S. G., Chang, A. n., Hingorani, S. R., Lee, D. n., Hwang, J. H. 2018; 34 (3): 284–91


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 delivery using mild hyperthermia in combination with the systemic administration of a low-temperature sensitive liposomal formulation of doxorubicin (LTSL-Dox) using a relevant model for pancreas cancer.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 hyperthermia and monitor therapy. Post-therapy, total Dox concentration in tumour tissue was determined by HPLC and confirmed with fluorescence microscopy.Localized hyperthermia was successfully applied and monitored with a clinical MR-HIFU system. The mild hyperthermia heating algorithm administered by the MR-HIFU system resulted in homogenous heating within the region of interest. MR-HIFU, in combination with LTSL-Dox, resulted in a 23-fold increase in the localised drug concentration and nuclear uptake of doxorubicin within the tumour tissue of KPC mice compared to LTSL-Dox alone. Hyperthermia, in combination with free Dox, resulted in a 2-fold increase compared to Dox alone.This study demonstrates that HIFU-induced hyperthermia in combination with LTSL-Dox can be a non-invasive and effective method in enhancing the localised delivery and penetration of doxorubicin into pancreatic tumours.

View details for DOI 10.1080/02656736.2017.1336675

View details for PubMedID 28715967

View details for PubMedCentralID PMC6135238