Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model

Abstract

Purpose Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently being used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two. Materials and Methods Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm 2 using a 0.5-MHz single-element transducer. The 633-nm laser was illuminated at 100 J/cm 2 . Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3. Results A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group ( p <0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG ( p <0.001) and Caspase-3 ( p <0.001), were observed in the SPDT group compared to other groups in IHC. Conclusion Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.

Glioblastoma Therapy: Past, Present and Future

“…Recent advances in PDT-GB research are as follows: (1) coupled NIR and photo immunotherapy (NIR-PIT), where a photosensitizer is conjugated to a highly specific monoclonal antibody [ 1043 , 1044 , 1045 ]; (2) NP-based PDT to augment systemic therapies and avoid skin photosensitization [ 1046 , 1047 ]; (3) NP-based PDT linked to miRNA or other chemotherapeutic agents [ 1048 ]; (4) strategies to increase PDT efficacy in hypoxic TME conditions [ 1049 , 1050 , 1051 , 1052 ]. Although some studies have demonstrated the enhanced penetration of light by simultaneous application of ultrasounds [ 1053 ], combined effects of PDT and SDT did not show any benefit in glioma rat models [ 1054 ].…”