Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 73, Issue -, Pages 239-251Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2014.05.003
Keywords
Oxymetry; Blood flow; Vascular-targeted PDT; Bacteriochlorins; Hydroxyl radical; Singlet oxygen; Superoxide; Phototoxicity; Photodynamic therapy; Free radicals
Funding
- Ministry of Science and Higher Education: Iuventus Plus [IP2011009471]
- European Union [POIG.02.01.00-12-023/08, POIG.02.01.00-12-064/08]
- National Science Center [2012/05/B/5T5/00389, DEC-2011/03/N/N24/02019]
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Blood flow and pO(2) changes after vascular-targeted photodynamic therapy (V-PDT) or cellular-targeted PDT (C-PDT) using 5,10,15,20-tetralds(2,6-difluoro-3-N-methylsulfamoylphenyl) bacteriochlorin (F(2)BMet) as photosensitizer were investigated in DBA/2 mice with S91 Cloudman mouse melanoma, and correlated with long-term tumor responses. F(2)BMet 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 pO(2) 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 pO(2), although the microcirculatory blood flow increased. Strong hypoxia after V-PDT led to a slight increase in VEGF level 24 h 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 pO(2) compensatory effects and modest tumor inhibition, but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition. (C) 2014 Elsevier Inc. All rights reserved.
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