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

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.

Combined photodynamic and radiodynamic therapy with a chlorine photosensitizer under fractionated radiation exposure to transplanted tumors in an <i>in vivo</i> experiment

“…Лесной, Республика Беларусь) в 2022 г., были направлены на изучение радиомодифицирующих свойств белорусского ФС, представляющего собой тринатриевую соль хлорина е6, при его комбинированном применении с ионизирующим излучением в однократном режиме воздействия в разовых очаговых дозах (РОД) 2, 4 и 6 Гр. Пилотные данные, полученные на основании анализа непосредственных и отдаленных результатов экспериментального исследования на крысах с лимфосаркомой Плисса (ЛСП), свидетельствовали о тенденции к достижению более выраженного противоопухолевого эффекта комбинированного лечения, включающего применение ФС с последующим проведением сеансов ЛТ в РОД 4 и 6 Гр, по сравнению с ЛТ в монорежиме [9]. Открытым остается вопрос применения ФС и ЛТ во фракционированном режиме облучения.…”

Radiodynamic Therapy with Photosensitizers: Mini-Review of Experimental and Clinical Studies

“…As modifiers that selectively enhance sensitivity of tumor cells to ionizing radiation, various physical and chemical effects are used: hyperbaric oxygenation, local and general hypoxia, electron-acceptor compounds, artificial hyperglycemia, local and wholebody hyperthermia, etc. The use of radiomodifiers (radiosensitizer, RS) makes it possible to increase the radiosensitivity of tumor cells located in hypoxic zones of the tumor, without increasing the degree of radiation damage to normal oxygenated cells [1].…”