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Free Radic Biol Med. 2014 Aug;73:239-51. doi: 10.1016/j.freeradbiomed.2014.05.003. Epub 2014 May 14.

The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy.

Author information

1
Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.
2
Faculty of Chemistry, Jagiellonian University, 30-060 Krakow, Poland. Electronic address: jdabrows@chemia.uj.edu.pl.
3
Chemistry Department, University of Coimbra, 3004-535 Coimbra, Portugal; Luzitin SA, 3045-016 Coimbra, Portugal. Electronic address: lgarnaut@ci.uc.pt.
4
Faculty of Chemistry, Jagiellonian University, 30-060 Krakow, Poland.
5
Faculty of Biochemistry, Biophysics, and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland. Electronic address: martyna.elas@uj.edu.pl.

Abstract

Blood flow and pO2 changes after vascular-targeted photodynamic therapy (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetrakis(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F2BMet) as photosensitizer were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F2BMet generates both singlet oxygen and hydroxyl radicals under near-infrared radiation, which consume oxygen. Partial oxygen pressure was lowered in PDT-treated tumors and this was ascribed both to oxygen consumption during PDT and to fluctuations in oxygen transport after PDT. Similarly, microcirculatory blood flow changed as a result of the disruption of blood vessels by the treatment. A novel noninvasive approach combining electron paramagnetic resonance oximetry and laser Doppler blood perfusion measurements allowed longitudinal monitoring of hypoxia and vascular function changes in the same animals, after PDT. C-PDT induced parallel changes in tumor pO2 and blood flow, i.e., an initial decrease immediately after treatment, followed by a slow increase. In contrast, V-PDT led to a strong and persistent depletion of pO2, although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase in VEGF level 24h after treatment. C-PDT caused a ca. 5-day delay in tumor growth, whereas V-PDT was much more efficient and led to tumor growth inhibition in 90% of animals. The tumors of 44% of mice treated with V-PDT regressed completely and did not reappear for over 1 year. In conclusion, mild and transient hypoxia after C-PDT led to intense pO2 compensatory effects and modest tumor inhibition, but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition.

KEYWORDS:

Bacteriochlorins; Blood flow; Free radicals; Hydroxyl radical; Oxymetry; Photodynamic therapy; Phototoxicity; Singlet oxygen; Superoxide; Vascular-targeted PDT

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