Radiodynamic Therapy with Chlorine-Based Photosensitizer on Pliss Lymphosarcoma Solid Tumor: In Vivo Experiment
DOI:
https://doi.org/10.30683/1927-7229.2022.11.05Keywords:
Chlorine-based photosensitizer, radiation therapy, radiodynamic therapy, laboratory animals, Pliss lymphosarcomaAbstract
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.
References
Takahashi J, Nagasawa S, Ikemoto MJ, et al. Verification of 5-aminolevurinic radiodynamic therapy using a murine melanoma brain metastasis model. Int J Mol Sci 2019; 20: 5155. https://doi.org/10.3390/ijms20205155 DOI: https://doi.org/10.3390/ijms20205155
Takahashi J, Nagasawa S, Doi M, et al. In vivo study of the efficacy and safety of 5-aminolevulinic radiodynamic therapy for glioblastoma fractionated radiotherapy. Int J Mol Sci 2021; 22: 9762. https://doi.org/10.3390/ijms22189762 DOI: https://doi.org/10.3390/ijms22189762
Yamamoto J, Ogura S, Shimajiri S, et al. 5-Aminolevulinic acidinduced protoporphyrin IX with multi-dose ionizing irradiation enhances host antitumor response and strongly inhibits tumor growth in experimental glioma in vivo. Mol Med Rep 2015; 11(3): 1813-19. https://doi.org/10.3892/mmr.2014.2991 DOI: https://doi.org/10.3892/mmr.2014.2991
Luksiene Z, Juzenas P, Moan J. Radiosensitization of tumours by porphyrins. Cancer Lett 2006; 235: 40-7. https://doi.org/10.1016/j.canlet.2005.03.041 DOI: https://doi.org/10.1016/j.canlet.2005.03.041
Schaffer M, Kulka U, Schaffer P. The role of radical derivatives of high reactivity in the radiosensitizing action of Photofrin II. J Porphyrins Phthalocyanines 2006; 10: 1398-1402. https://doi.org/10.1142/S1088424606000776 DOI: https://doi.org/10.1142/S1088424606000776
Tzerkovsky DA, Protopovich YaL, Kozlovsky DI, Suslova VA. Antitumor efficiency of contact radiotherapy in combination with a chlorin-based photosensitizer in experiment. Biomed Photonics 2021; 10(2): 25-33. https://doi.org/10.24931/2413-9432-2021-10-2-25-33 DOI: https://doi.org/10.24931/2413-9432-2021-10-2-25-33
Algorri JF, Ochoa M, Roldán-Varona P, et al. Photodynamic therapy: a compendium of latest reviews. Cancers (Basel) 2021; 13(17): 4447. https://doi.org/10.3390/cancers13174447 DOI: https://doi.org/10.3390/cancers13174447
Schaffer M, Schaffer PM, Jori G, et al. Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Tumori 2002; 88: 407-10. https://doi.org/10.1177/030089160208800511 DOI: https://doi.org/10.1177/030089160208800511
Schaffer M, Ertl-Wagner B, Schaffer PM, et al. Porphyrins as radiosensitizing agents for solid neoplasms. Curr Pharm Des 2003; 9(25): 2024-35. https://doi.org/10.2174/1381612033454153 DOI: https://doi.org/10.2174/1381612033454153
Rutkovskienė L, Plėšnienė L, Sendiulienė D, et al. Sensitization of rat C6 glioma cells to ionizing radiation by porphyrins. Acta Medica Lituanica 2011; 18(2): 56-62. https://doi.org/10.6001/actamedica.v18i2.1816 DOI: https://doi.org/10.6001/actamedica.v18i2.1816
Schaffer M, Kulka U, Ertl-Wagner B, et al. Effect of Photofrin II as a radio-sensitizing agent in two different oesophageal carcinoma cell lines. J Porphyrins Phthalocyanines 2005; 9: 470-75. https://doi.org/10.1142/S1088424605000587 DOI: https://doi.org/10.1142/S1088424605000587
Tzerkovsky DA. Photosensitizers as radiosensitizing agents in experimental and clinical neurooncology. Biomed Photonics 2017; 6(2): 27-33 (in Russian).
Moradi A, Hashemi B, Hassan Z. In vivo evaluation of photofrin II radiosensitivity for the treatment of adenocarcinoma tumors in balb/C mice using brachytherapy. IFMBE Proceedings 2009; 25(1): 141-43. https://doi.org/10.1007/978-3-642-03474-9_41 DOI: https://doi.org/10.1007/978-3-642-03474-9_41
Bloznelytė-Plėšnienė L, Rutkovskiene L. Radiosensitized treatment of primary or metastatical malignant brain tumors with hematoporphyrin derivative. Electron Electric Engineer 2006; 4(68): 83-6.
Schaffer M, Еrtl-Wagner В, Schaffer РМ. Feasibility of photofrin II as a radiosensitizing agent in solid tumors – preliminary results. Onkologie 2006; 29: 514-19. https://doi.org/10.1159/000095979 DOI: https://doi.org/10.1159/000095979
Schaffer М, Hofstetter А, Ertl-Wagner В, et al. Treatment of astrocytoma grade III with Photofrin II as a radiosensitizer. A case report. Strahlenther Onkol 2013; 189(11): 972-76. https://doi.org/10.1007/s00066-013-0430-2 DOI: https://doi.org/10.1007/s00066-013-0430-2
Schaffer Р, Batash R, Ertl-Wagner В, et al. Treatment of cervix carcinoma FIGO IIIb with Photofrin II as a radiosensitizer: a case report. Photochem Photobiol Sci 2019; 18: 1275-79. https://doi.org/10.1039/C8PP00576A DOI: https://doi.org/10.1039/C8PP00576A
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
