Saito Yuki, Fukami Shinjiro, Nagai Kenta, Ogawa Emiyu, Kuroda Masahiko, Kohno Michihiro, Akimoto Jiro
Department of Neurosurgery, Tokyo Medical University, Tokyo 160-0023, Japan.
Department of Electronics and Electrical Engineering, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Biomedicines. 2024 Sep 20;12(9):2141. doi: 10.3390/biomedicines12092141.
This preclinical study was conducted to investigate the efficacy of interstitial PDT (i-PDT) for malignant gliomas arising deep within the brain, which are difficult to remove. C6 glioma cells were implanted into the basal ganglia of rats, and 3 weeks later, the second-generation photosensitizer talaporfin sodium (TPS) was administered intraperitoneally. Ninety minutes after administration, a prototype fine plastic optical fiber was punctured into the tumor tissue, and semiconductor laser light was irradiated into the tumor from a 2-mm cylindrical light-emitting source under various conditions. The brain was removed 24 h after the i-PDT and analyzed pathologically. The optical fiber was able to puncture the tumor center in all cases, enabling i-PDT to be performed. Histological analysis showed that tumor necrosis was induced in areas close to the light source, correlating with the irradiation energy dose, whereas apoptosis was induced at some distance from the light source. Irradiation using high energy levels resulted in tissue swelling from strong tumor necrosis, and irradiation at 75 J/cm was most suitable for inducing apoptosis. An experimental system of i-PDT using TPS was established using malignant glioma cells transplanted into the rat brain. Tumor cell death, which correlated with the light propagation, was induced in tumor tissue.
本临床前研究旨在调查间质光动力疗法(i-PDT)对难以切除的脑深部恶性胶质瘤的疗效。将C6胶质瘤细胞植入大鼠基底神经节,3周后腹腔注射第二代光敏剂他拉泊芬钠(TPS)。给药90分钟后,将一根原型精细塑料光纤刺入肿瘤组织,并在各种条件下从2毫米圆柱形发光源向肿瘤照射半导体激光。i-PDT后24小时取出大脑并进行病理分析。在所有病例中,光纤均能刺入肿瘤中心,从而能够进行i-PDT。组织学分析表明,靠近光源的区域诱导了肿瘤坏死,这与照射能量剂量相关,而在距光源一定距离处诱导了细胞凋亡。高能量水平照射导致强烈的肿瘤坏死引起组织肿胀,75 J/cm的照射最适合诱导细胞凋亡。利用移植到大鼠脑内的恶性胶质瘤细胞建立了使用TPS的i-PDT实验系统。肿瘤组织中诱导了与光传播相关的肿瘤细胞死亡。