Experimental study to assess the efficacy and safety of therapeutic doses of the photosensitizer Chlorin E6 in a model of undifferentiated adenocarcinoma
Svechkova A.A.¹, Khamid A.Kh.¹, Zmitrichenko Yu.G.², Tochilnikov G.V.², Belyaev M.A.¹, Zakharenko A.A.¹
1Pavlov First Saint Petersburg State Medical University of the Ministry of Healthcare of Russian Federation, Saint Petersburg, Russian Federation
2Federal State Budgetary Institution «National Medical Research Center of Oncology named after N.N. Petrov» of the Ministry of Health of the Russian Federation, Saint Petersburg, Russian Federation
Brief summary
Chlorin e6 is a third-generation photosensitizer produced in the Russian Federation. Given the lack of data on optimal doses of Chlorin e6 for the treatment of adenocarcinomas and the official information on its wide therapeutic window (1.0 mg/kg - 2.5 mg/kg), it is promising to conduct an experimental study to evaluate the efficacy and safety of Chlorin e6 in adenocarcinoma treatment.
Objective. To assess the efficacy and safety of therapeutic doses of Chlorin e6 in a model of undifferentiated adenocarcinoma.
Materials and Methods. Forty Wistar rats were divided into three groups: maximum dose group (2.5 mg/kg Chlorin e6, n=13), minimum dose group (1.0 mg/kg, n=13), and control group (n=14). Rats received subcutaneous transplantation of undifferentiated adenocarcinoma cell suspension. Fourteen days post-transplantation, local tumor irradiation was performed. Animals were euthanized on days 1 and 3 post-irradiation (3 animals per group) and day 7 (2 animals per group); the remaining animals were observed until natural death. The primary endpoint was the degree of tumor histopathological regression. Secondary endpoints included tumor volume, necrosis volume within the tumor, growth/regression coefficient, fluorescence intensity, contrast index, overall survival, and toxicity assessment of different Chlorin e6 doses.
Results. On day 5, tumor volume in the minimum dose group was significantly lower than in the maximum dose group (p=0.028). Tumor growth coefficient on day 3 was also lower in the minimum dose group (p=0.011). Fluorescence differences were significant overall (p=0.001) but absent between experimental groups (p=0.864). Contrast index, necrosis volume, and histopathological parameters did not differ significantly (p>0.05). The degree of histopathological regression varied among all groups but not between experimental doses (p=0.569). Toxicity profiles were comparable.
Conclusions. The minimal therapeutic dose of Chlorin e6 during photodynamic therapy yields a more effective clinical response while maintaining histopathological regression and toxicity profiles comparable to the maximum dose. These findings support the use of minimal therapeutic doses of Chlorin e6 in photodynamic therapy for adenocarcinoma to enhance treatment efficacy and safety and reduce economic costs. Further clinical studies are warranted.
1. Dolan M.E., et al. Photodynamic therapy in cancer: An update. Photodiagnosis and Photodynamic Therapy. 2017; 17: 121-5. https://doi.org/10.1016/j.pdpdt.2017.04.003
2. Agostinis P., et al. Photodynamic therapy of cancer: An update. CA: A Cancer Journal for Clinicians. 2011; 61(4): 250-81. https://doi.org/10.3322/caac.20114
3. Oser M., et al. Photodynamic therapy for cancer treatment. International Journal of Molecular Sciences. 2017; 18(1) : 65. https://doi.org/10.3390/ijms18010065
4. Goto Y., Sakurai T. Clinical applications of photodynamic therapy for oral cancer. Cancers (Basel). 2020; 12(5) : 1242. https://doi.org/10.3390/cancers12051242
5. Peng H., et al. Current status and future outlook of photodynamic therapy. Nanomaterials. 2017; 7(12) : 458. https://doi.org/10.3390/nano7120458
6. Joseph B., Mauramo M., Vijayakumary B.K., Waltimo T., Anil S., Sorsa T. Photodynamic therapy for oral mucositis in cancer patients — a systematic review and meta-analysis. Photodiagnosis and Photodynamic Therapy. 2024; 50:104424. https://doi.org/10.1016/j.pdpdt.2024.104424
7. Pogarceva U.A., Kayhova I.E. Polychenie i standartizaciya opitnih partii lekarstvennogo preparata dlya fotodinamicheskoi terapii «Fotoran E6, liofilizat dlya prigotovleniya rastvora dlya infyzii» s ispolzovaniem v kachestve sirya listev borshevika. Voprosi biologicheskoi, medicinskoi i farmacevticheskoi himii. 2024; 27(7) : 11−15. https://doi.org/10.29296/25877313-2024-07-02
8. Abramova O.B., Kaplan M.A., Ujakov V.V., Drojjina V.V., Bandyrko L.N., Yakovleva N.D., i dr. Protivoopyholevaya effektivnost fotodinamicheskoi terapii karcinomi Erliha mishei s novim fotosensibilizatorom Fotoran E6. Radiaciya i risk. 2022; 31(2): 162-73. https://doi.org/10.21870/0131-3878-2022-31-2-162-173
10. Abramova O.B., Drojjina V.V., Kozlovceva E.A., Sivolova T.P., Kaprin A.D. Vozdeistvie fotodinamicheskoi terapii s fotosensibilizatorom Fotoran E6 na melanomy V-16 i reakciya perifericheskoi krovi mishei. Radiaciya i risk. 2022; 31(2): 162-73. https://doi.org/10.21870/0131-3878-2022-31-2-162-173
11. Kapinys V. N., Kaplan M. A., Yaroslavceva-Isaeva E. V., Spichenkova I. S., Ivanov S. A. Primenenie hlorin E6-fotodinamicheskoi terapii bazalno-
kletochnogo raka koji. Issledovaniya i praktika v medicine. 2021; 8(4): 33-43. https://doi.org/10.17709/2410-1893-2021-8-4-3
12. Aebisher D., Szpara J., Bartusik-Aebisher D. Advances in medicine: photodynamic therapy. International Journal of Molecular Sciences. 2024; 25(15): 8258. https://doi.org/ 10.3390/ijms25158258
13. Kolarikova M., et al. Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments. Medicinal Research Reviews. 2023; 43(4): 717-74. https://doi.org/10.1002/med.21935.