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

Abstract

Introduction. The current direction of scientific research in experimental and clinical oncology is radiodynamic therapy (RDT), a treatment method based on the activation of photosensitizers (PS) by ionizing radiation. As the results of in vitro / in vivo studies show, a number of photosensitizing agents have radiomodifying properties, and the method itself is characterized by high antitumor efficacy. Aim. To study the possibility of increasing the effectiveness of photodynamic therapy (PDT) through its combined use with RDT in an in vivo experiment. Materials and methods. The work was performed on 26 white non-linear rats weighing 180 ± 50 g. Pliss lymphosarcoma was used as a tumor model, which was transplanted subcutaneously. The chlorine-based PS (Belmedpreparaty, Republic of Belarus) was administered intravenously at a dose of 2.5 mg / kg of body weight. The RDT session was performed by the contact method (CRT) after 2.5–3, 24 and 48 hours after the end of PS administration on the microSelectron-HDR V3 Digital device (Elekta, Sweden) using γ-radiation (192Ir) in a single focal dose (SFD) of 2 Gy until the total focal dose of 6 Gy is reached. A PDT session was performed once immediately after the first exposure to ionizing radiation using a PDT diode laser (Imaf Axicon, Republic of Belarus, λ = 660 ± 5 nm) at an exposure dose of 100 J / cm² with a power density of 0.2 w / cm² and a power of 0.353 w. All rats were divided into 4 groups of 6–7 animals each: intact control, PS + PDT, PS + CRT, PS + CRT + PDT. The criteria for evaluating antitumor efficacy were: the average volume of tumors (Vav), the coefficient of absolute growth of tumors (K), the coefficient of tumor growth inhibition (TGI), the frequency of complete tumor regressions (CR), the proportion of cured rats, an increase in the average duration of dead rats. Differences were considered statistically significant at p <0.05. Results. On the 18th day of the experiment, Vav in groups was 65.98 ± 0.81 cm³; 24.02 ± 4.01 cm³ (р <0.00001); 17.11 ± 4.13 cm³ (р <0.00001); 4.42 ± 1.65 cm³ (р <0.00001), respectively. Coefficients K – 5497.33 OE; 1714.71 OE; 1424.83 OE; 367.33 OE. TGI coefficients – 63.60 % (PS + PDT); 74.07 % (PS + CRT); 93.30 % (PS + CRT + PDT). An in crease in the average duration of dead rats indicator – 25.31 % (PS + PDT); 55.06 % (PS + CRT); 158.22 % (PS + CRT + PDT). On the 60th and 90th days of the experiment, the frequency of CR and the proportion of cured rats were the same and amounted to 0; 16.7; 14.3 and 42.9 %, respectively. Conclusion. The results obtained indicate that the chlorine PS has, in addition to photosensitizing properties, also radiomodifying properties, and the developed method of combined therapy is characterized by high antitumor efficacy.