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

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.

• Authors: Martyna Krzykawska-Serda, Janusz M Dąbrowski, Luis G Arnaut, Małgorzata Szczygieł, Krystyna Urbańska, Grażyna Stochel, Martyna Elas
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 73 Pg. 239-51 (Aug 2014) ISSN: 1873-4596 [Electronic] United States
• PMID: 24835769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Photosensitizing Agents
• Porphyrins
• Reactive Oxygen Species
• Vascular Endothelial Growth Factor A
• bacteriochlorin
• vascular endothelial growth factor A, mouse
• Oxygen

Topics

• Animals
• Apoptosis
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Male
• Melanoma (blood supply, metabolism, therapy)
• Mice
• Mice, Inbred DBA
• Microcirculation (drug effects)
• Oxygen (metabolism)
• Oxygen Consumption (drug effects)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacology)
• Porphyrins (pharmacology)
• Reactive Oxygen Species
• Vascular Endothelial Growth Factor A (metabolism)