Nagai Kenta, Akimoto Jiro, Fukami Shinjiro, Saito Yuki, Ogawa Emiyu, Takanashi Masakatsu, Kuroda Masahiko, Kohno Michihiro
Department of Neurosurgery, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-Ku, Tokyo, 160-0023, Japan.
Faculty of Science and Technology, Keio University, Kanagawa, Japan.
Sci Rep. 2024 Apr 21;14(1):9137. doi: 10.1038/s41598-024-59955-y.
To investigate the therapeutic potential of photodynamic therapy (PDT) for malignant gliomas arising in unresectable sites, we investigated the effect of tumor tissue damage by interstitial PDT (i-PDT) using talaporfin sodium (TPS) in a mouse glioma model in which C6 glioma cells were implanted subcutaneously. A kinetic study of TPS demonstrated that a dose of 10 mg/kg and 90 min after administration was appropriate dose and timing for i-PDT. Performing i-PDT using a small-diameter plastic optical fiber demonstrated that an irradiation energy density of 100 J/cm or higher was required to achieve therapeutic effects over the entire tumor tissue. The tissue damage induced apoptosis in the area close to the light source, whereas vascular effects, such as fibrin thrombus formation occurred in the area slightly distant from the light source. Furthermore, when irradiating at the same energy density, irradiation at a lower power density for a longer period of time was more effective than irradiation at a higher power density for a shorter time. When performing i-PDT, it is important to consider the rate of delivery of the irradiation light into the tumor tissue and to set irradiation conditions that achieve an optimal balance between cytotoxic and vascular effects.
为了研究光动力疗法(PDT)对不可切除部位发生的恶性胶质瘤的治疗潜力,我们在皮下植入C6胶质瘤细胞的小鼠胶质瘤模型中,研究了使用替莫泊芬钠(TPS)的间质光动力疗法(i-PDT)对肿瘤组织损伤的影响。对TPS的动力学研究表明,给药后10mg/kg的剂量和90分钟是i-PDT合适的剂量和时间。使用小直径塑料光纤进行i-PDT表明,需要100J/cm或更高的照射能量密度才能在整个肿瘤组织上实现治疗效果。组织损伤在光源附近区域诱导细胞凋亡,而在距光源稍远的区域发生血管效应,如纤维蛋白血栓形成。此外,当以相同能量密度照射时,较低功率密度较长时间的照射比较高功率密度较短时间的照射更有效。进行i-PDT时,重要的是要考虑照射光进入肿瘤组织的输送速率,并设置在细胞毒性和血管效应之间实现最佳平衡的照射条件。