Intratumoral radiofrequency hyperthermia-enhanced chemotherapy of liposomal doxorubicin on hepatocellular carcinoma.

purposeTo investigate the possibility of using radiofrequency hyperthermia (RFH) to enhance intratumoral therapeutic effect of liposomal doxorubicin on hepatocellular carcinoma (HCC) via an interventional molecular imaging approach. MATERIALS AND

methodsFor both in-vitro confirmation and in-vivo validation, Luciferase/mCherry-labeled human HCC cells (HepG2) and mice subcutaneous hepatic cancer xenografts were treated by: (i) combination therapy of liposomal doxorubicin plus RFH at 42°C; (ii) liposomal doxorubicin alone; (iii) RFH at 42°C alone; (iv) phosphate buffered saline (PBS) as a control. For in-vitro confirmation, MTS assay, confocal microscopy, optical imaging and flow cytometry were used to evaluate and compare cell viabilities and apoptosis among different treatment groups. For in vivo validation, liposomal doxorubicin was directly injected into the tumor and RFH was performed subsequently under ultrasound imaging guidance. Changes of tumor sizes were quantified using ultrasound imaging and bioluminescence signal intensities after treatments were measured by optical imaging over 14 days, which were correlated with subsequent histology analysis.

resultsOf in vitro experiments, MTS assay demonstrated the lowest cell proliferation in combination therapy group compared with the other three groups (25.0 ± 5.6% vs 49.7 ± 5.2% vs 94.2 ± 3.9% vs 100%, respectively,

conclusionRFH can enhance intratumoral therapy with liposomal doxorubicin for HCC, which is effectively monitored by ultrasound imaging and optical imaging techniques. This concept may provide new avenues for eradicating the residual tumor cells when combining RFA with interventional molecular imaging guided direct intratumoral chemotherapy of HCC.