Effect of tumor host microenvironment on photodynamic therapy in a rat prostate tumor model.
Abstract | PURPOSE: EXPERIMENTAL DESIGN: RESULTS: Orthotopic MatLyLu tumors were found to grow faster, have higher vessel density and more permeable vasculature, have higher vascular endothelial growth factor protein levels, and have lower tumor hypoxic fraction than the s.c. tumors. Uptake of photosensitizer verteporfin in the orthotopic tumor was higher than in the s.c. tumors at 15 minutes after injection (1 mg/kg, i.v.), and became similar at 3 hours after injection. For the vascular targeting PDT treatment (0.25 mg/kg verteporfin, 50 J/cm(2) at 50 mW/cm(2), 15 minutes drug-light interval), there was no significant difference in PDT-induced tumor necrotic area between the orthotopic and s.c. tumors, with 85% to 90% necrosis in both types of tumors. However, tumor necrosis induced by the cellular targeting PDT (1 mg/kg verteporfin, 50 J/cm(2) at 50 mW/ cm(2), 3 hours drug-light interval) was significantly different in the orthotopic (64%) versus the s.c. (29%) tumors. CONCLUSIONS:
Tumor host environment can significantly affect photosensitizer verteporfin distribution and PDT treatment effect. Verteporfin- PDT regimen targeting tumor cells is more sensitive to such influence than the vascular targeting PDT. Our study showed the importance of tumor host environment in determining tumor physiologic properties and tumor response to PDT. To obtain clinically relevant information, orthotopic tumor model should be used in the experimental studies.
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Authors | Bin Chen, Brian W Pogue, Xiaodong Zhou, Julia A O'Hara, Nicolas Solban, Eugene Demidenko, P Jack Hoopes, Tayyaba Hasan |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 11
Issue 2 Pt 1
Pg. 720-7
(Jan 15 2005)
ISSN: 1078-0432 [Print] United States |
PMID | 15701861
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Photosensitizing Agents
- Porphyrins
- Vascular Endothelial Growth Factor A
- vascular endothelial growth factor A, mouse
- Verteporfin
- Oxygen
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Topics |
- Animals
- Disease Models, Animal
- Lung Neoplasms
(blood supply, drug therapy, secondary)
- Lymphatic Metastasis
- Lymphocytes, Tumor-Infiltrating
(drug effects)
- Macrophages
(drug effects)
- Male
- Neovascularization, Pathologic
(drug therapy, metabolism)
- Oxygen
(metabolism)
- Photochemotherapy
- Photosensitizing Agents
(pharmacokinetics, therapeutic use)
- Porphyrins
(pharmacokinetics, therapeutic use)
- Prostatic Neoplasms
(blood supply, drug therapy, pathology)
- Rats
- Regional Blood Flow
- Skin Neoplasms
(blood supply, drug therapy)
- Vascular Endothelial Growth Factor A
(metabolism)
- Verteporfin
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