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

 Junwon Park  ;  Chanho Kong  ;  Jaewoo Shin  ;  Ji Young Park  ;  Young Cheol Na  ;  Seung Hee Han  ;  Jin Woo Chang  ;  Seung Hyun Song  ;  Won Seok Chang 
 YONSEI MEDICAL JOURNAL, Vol.64(4) : 233-242, 2023-04 
Journal Title
Issue Date
Animals ; Brain Neoplasms* / diagnostic imaging ; Brain Neoplasms* / drug therapy ; Caspase 3 ; Cell Line, Tumor ; Glioblastoma* / diagnostic imaging ; Glioblastoma* / drug therapy ; Glioma* / diagnostic imaging ; Glioma* / drug therapy ; Photochemotherapy* / methods ; Rats ; Rats, Sprague-Dawley ; Ultrasonic Therapy* / methods
Focused ultrasound ; glioblastoma ; photodynamic therapy ; sono-photodynamic therapy ; sonodynamic therapy ; treatment
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 be ing 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/cm2 using a 0.5-MHz single-element transducer. The 633-nm laser was illumi nated at 100 J/cm2. 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.
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1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kong, Chanho(공찬호)
Shin, Jaewoo(신재우) ORCID logo https://orcid.org/0000-0002-6335-1292
Chang, Won Seok(장원석) ORCID logo https://orcid.org/0000-0003-3145-4016
Chang, Jin Woo(장진우) ORCID logo https://orcid.org/0000-0002-2717-0101
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