Radiodynamic Therapy with Chlorine-Based Photosensitizer on Pliss Lymphosarcoma Solid Tumor: In Vivo Experiment

D. Tzerkovsky, A. Mazurenko, D. I. Kozlovsky, F.F. Borychevsky
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引用次数: 2

Abstract

The aim of this study was to investigate the antitumor efficacy of radiodynamic therapy (RDT) with a chlorin-based photosensitizer (PS) in an in vivo experiment. Material and Methods: The study was performed in 35 white outbred rats weighing 180±30 g. Subcutaneously transplanted Pliss lymphosarcoma (PLS) was used as tumor model. Chlorin-based PS «Photolon» (RUE «Belmedpreparaty», Republic Belarus) was injected intravenously at a dose of 2.5 mg/kg. The radiation therapy sessions (RT) were carried out once 2.5–3 hours after the administration of the PS by the contact method on the device «microSelectron-HDR V3 Digital» (Elekta, Sweden) using γ-radiation (192Ir) in single focal doses (SFD) 2, 4 and 6 Gy. All laboratory animals were subdivided into 7 groups of 5 animals each: intact control, RT 2 Gy, RT 4 Gy, RT 6 Gy, PS + RT 2 Gy, PS + RT 4 Gy and PS + RT 6 Gy. The antitumor effectiveness of exposure was evaluated according to the indicators characterizing the dynamics of volume changes: Vav. (cm3), the coefficient of absolute tumor growth (K, units) and the coefficient of tumor growth inhibition (TGI, %). The frequency of complete regressions (СR) was estimated 60 days after the performed exposures. In each group, the share of animals (%) with no visual and palpatory signs of tumor growth was evaluated. The differences were considered statistically significant at the significance level of p<0.05. Results: On the 16th day from the beginning of the experiment Vav. in groups were 39.07±4.19; 23.06±3.25 (р=0.012); 35.04±2.35 (р=0.419); 25.83±3.06 (р=0.027); 28.36±3.45 (0.074); 25.47±1.88 (р=0.013) and 16.56±3.64 cm3 (р=0,002), respectively. The K coefficients in the experimental groups were 1219.94; 657.86; 1296.78; 716.50; 833.12; 669.26 and 590.43 units, respectively. The TGI coefficients in the experimental groups were 40.98%; 10.31%; 33.89%; 27.41%; 34.81% and 57.61%, respectively. The frequency of complete tumor regressions 60 days after the start of the experiment was 0%, 20%, 0%, 0%, 0%, 0% and 40%, respectively. Conclusion: RDT is a recent extension of conventional photodynamic therapy, in which visible/near infrared light irradiation is replaced by a well-tolerated dose of X-rays. Systemic administration of chlorin-based PS before the RT session increases the antitumor efficacy of RT in animals with PLS transplantable tumors. The data obtained indicate that further studies of the radiosensitizing properties of PS are promising.
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氯基光敏剂放射动力学治疗Pliss淋巴肉瘤实体瘤:体内实验
本研究旨在探讨氯基光敏剂(PS)放射动力治疗(RDT)的体内抗肿瘤效果。材料与方法:选用35只体重180±30 g的纯种大鼠。以皮下移植Pliss淋巴肉瘤(PLS)为肿瘤模型。氯基PS«Photolon»(RUE«Belmedpreparaty»,白俄罗斯共和国)以2.5 mg/kg的剂量静脉注射。放射治疗(RT)在PS给药后2.5-3小时,通过接触法在装置«microselecon - hdr V3 Digital»(Elekta,瑞典)上使用单焦剂量(SFD) 2、4和6 Gy的γ辐射(192Ir)进行一次。所有实验动物再分为7组,每组5只:完整对照、RT 2 Gy、RT 4 Gy、RT 6 Gy、PS + RT 2 Gy、PS + RT 4 Gy和PS + RT 6 Gy。根据表征体积变化动态的指标:Vav来评价暴露的抗肿瘤效果。(cm3)、肿瘤绝对生长系数(K,单位)和肿瘤生长抑制系数(TGI, %)。完全回归的频率(СR)是在暴露后60天估计的。在每一组中,评估没有视觉和触诊肿瘤生长迹象的动物比例(%)。以p<0.05的显著性水平为差异有统计学意义。结果:实验开始后第16天,大鼠肝细胞凋亡。各组分别为39.07±4.19;23.06±3.25(р= 0.012);35.04±2.35(р= 0.419);25.83±3.06(р= 0.027);28.36±3.45 (0.074);分别为25.47±1.88 cm3(±0.013)和16.56±3.64 cm3(±0.002)。试验组K系数为1219.94;657.86;1296.78;716.50;833.12;分别为669.26和590.43个单位。试验组TGI系数为40.98%;10.31%;33.89%;27.41%;分别为34.81%和57.61%。实验开始后60天肿瘤完全消退的频率分别为0%、20%、0%、0%、0%、0%、0%和40%。结论:RDT是传统光动力疗法的最新延伸,其中可见光/近红外光照射被耐受良好的x射线剂量所取代。在放射治疗前全身给予氯基PS,可增加具有PLS可移植肿瘤的动物的放射治疗的抗肿瘤疗效。所获得的数据表明,进一步研究PS的放射增敏特性是有希望的。
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