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|Title:||The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy||Authors:||Krzykawska-Serda, Martyna
Dąbrowski, Janusz M.
Arnaut, Luis G.
|Keywords:||Oxymetry; Blood flow; Vascular-targeted PDT; Bacteriochlorins; Hydroxyl radical; Singlet oxygen; Superoxide; Phototoxicity; Photodynamic therapy; Free radicals||Issue Date:||Aug-2014||Publisher:||Elsevier||Citation:||KRZYKAWSKA-SERDA, Martyna [et. al] - The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy. "Free Radical Biology and Medicine". ISSN 0891-5849. Vol. 73 (2014) p. 239–251||Serial title, monograph or event:||Free Radical Biology and Medicine||Volume:||73||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 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 pO2 compensatory effects and modest tumor inhibition, but strong and persistent local hypoxia after V-PDT caused tumor growth inhibition.||URI:||http://hdl.handle.net/10316/27908||ISSN:||0891-5849||DOI:||10.1016/j.freeradbiomed.2014.05.003||Rights:||openAccess|
|Appears in Collections:||FCTUC Química - Artigos em Revistas Internacionais|
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