Affiliation:
1. P.A. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Center of Radiology
2. SSC “NIOPIK”
Abstract
Introduction. Special attention has been recently paid to photosensitizers that absorb and fluoresce in the near infrared region of the spectrum. One of the most promising photosensitizers is bacteriosens, a synthetic bacteriochlorin derivative. Objective. To conduct a preclinical study of the biodistribution and pharmacokinetics of bacteriosens in animals.Materials and methods. The active ingredient of bacteriosens is (meso-tetra(3-pyridyl)bacteriochlorin) with of λmax 747 nm). The biodistribution and pharmacokinetics of the agent were studied in mice and rabbits. It was administered intravenously once at three doses: 1.0; 2.5 and 6.25 mg/kg for the mice and 0.236; 0.59 and 1.475 mg/kg for the rabbits. Local fluorescence spectroscopy was used for the quantitative determination of the pharmacokinetic parameters of bacteriosens.Results. Bacteriosens was removed quickly from the mouse bloodstream at 1 and 4 days after using minimal (1.0 mg/kg) and maximal (6.25 mg/kg) doses, respectively. When given at doses of 6.25 mg/kg and 1.0 mg/kg, bacteriosens was recorded in the skin, muscle, and spleen for 4 days and 24 h, respectively. The agent most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (6.25 mg/kg) and 2 days (1.0 mg/kg). A similar pattern was observed in the rabbits. Bacteriosens was rapidly removed from the rabbit bloodstream at 1 and 3 days after using at doses of 0.236 and 1.475 mg/kg, respectively. The agent was recorded in the skin, muscle, and spleen up to 4 days (1.475 mg/kg) and 3 days (0.236 mg/kg). It most intensively accumulated and long persisted in the omentum, liver, and kidneys for more than 6 days (1.475 mg/kg) and 4 days (0.236 mg/kg).Conclusion. Bacteriosens was removed from the animal bloodstream within 3–4 days after administration of the maximum dose that was 2.5 times higher than therapeutic one. The half-life of bacteriosens for mice was directly proportional to the dose and increased from 8 to 24 min; the half-life for rabbits was 20 min, irrespective of the dose. The drug was recorded in the skin for no more than 4 days. The main routes of bacteriosens elimination from the body of animals were the kidneys and liver.The study was performed in accordance with ethical principles adopted by the European Convention for the protection of vertebrate animals used for experimental and other scientific purposes.
Publisher
Publishing House ABV Press
Reference12 articles.
1. Filonenko E.V. Fluorescence diagnostics and photodynamic therapy: justification of applications and opportunities in oncology. Fotodinamicheskaya terapiya i fotodiagnostika = Photodynamic therapy and photodiagnosis 2014;1:3–8. (In Russ.).
2. Shafirstein G., Bellnier D., Oakley E. et al. Interstitial Photodynamic Therapy-A Focused Review. Cancers (Basel) 2017;9(2):12. DOI: 10.3390/cancers9020012.
3. Chilakamarthi U., Giribabu L. Photodynamic therapy: past, present and future. Chem Rec 2017;17(8):775–802. DOI: 10.1002/tcr.201600121.
4. Mironov A.F., Grin M.A. Bacteriochlorin sensitizers: prospects of use in photodynamic therapy. Vestnik MITHT 2006;4:5–28. (In Russ.).
5. Krzykawska-Serda M., Dąbrowski J.M., Arnaut L.G. et al. The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy. Free Radic Biol Med 2014;73:239–51. DOI: 10.1016/j.freeradbiomed. 2014.05.003.