The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy
The role of strong hypoxia in tumors after treatment in the outcome of bacteriochlorin-based photodynamic therapy
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DOI：
10.1016/j.freeradbiomed.2014.05.003
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发表时间：
2014-08-01
影响因子：
7.4
通讯作者：
Elas, Martyna
中科院分区：
文献类型：
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作者：
Krzykawska-Serda, Martyna;Dabrowski, Janusz M.;Elas, Martyna
研究了DBA/2小鼠S91 Cloudman黑色素瘤血管靶向光动力疗法（V-PDT）和细胞靶向光动力疗法（C-PDT）后血流量和pO（2）的变化，并与肿瘤的长期反应进行了相关性分析。F（2）BMet在近红外辐射下产生单线态氧和羟基自由基，它们消耗氧。PDT治疗的肿瘤中氧分压降低，这归因于PDT过程中的氧消耗和PDT后氧转运的波动。同样，微循环血流量由于治疗对血管的破坏而发生变化。一种新的非侵入性的方法相结合的电子顺磁共振血氧饱和度和激光多普勒血流灌注测量允许纵向监测缺氧和血管功能的变化，在相同的动物，PDT后。C-PDT诱导肿瘤pO（2）和血流的平行变化，即，治疗后立即开始下降，随后缓慢上升。相比之下，V-PDT导致pO（2）的强烈和持久的耗竭，尽管微循环血流量增加。V-PDT治疗后24 h，V-PDT治疗后较强的缺氧导致VEGF水平略有升高。C-PDT引起了CA。5-V-PDT在肿瘤生长中的作用比V-PDT有效得多，并且在90%的动物中导致肿瘤生长抑制。用V-PDT治疗的44%的小鼠的肿瘤完全消退，并且超过1年没有再出现。总之，C-PDT后轻度和短暂的缺氧导致强烈的pO（2）代偿效应和适度的肿瘤抑制，但V-PDT后强烈和持续的局部缺氧导致肿瘤生长抑制。(C)2014 Elsevier Inc. All rights reserved.
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.