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.
Photodynamic Therapy (PDT) is a light-based method that uses photo-reactive molecules, such as different types of photosensitizers (PS), to destroy malignant tumors. As some authors testify, PS was shown to act as a radio-reactive molecule by enhancing generation of reactive oxygen species upon X-ray irradiation. The method of treatment, which is based on the combined use of PS and ionizing radiation, is called «Radiodynamic therapy» (RDT). The advantage of RDT over PDT is the X-ray’s penetrability through tissues, which will find many applications for treatment of deep malignant tumors. The authors of a number of research centers in Japan, Germany, Israel and Lithuania presented the experience of using RDT in experiments on tumor cell lines and animals with transplanted tumors. A clinical approbation of the method has been started in patients with unresectable forms of bladder and cervical cancer, with gliomas and other forms of malignant tumors. The data obtained in experiments on cultures of tumor cells and animals with transplanted tumors indicate a high antitumor efficacy of the RDT with various types of PS. This fact is confirmed by a statistically significant decrease in viable tumor cells with the combined use of RT and PS, as well as a pronounced inhibition of the growth of transplanted tumors compared with the control groups, including the group of radiation therapy in mono mode. The preliminary data obtained show good tolerability of the method in clinical oncology (no serious adverse reactions) and satisfactory antitumor efficacy (an increase in the frequency of objective responses and an increase in the % reduction in tumor volume, which made it possible to transfer them to a resectable state).
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