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Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre‐treated by photodynamic therapy
Author(s) -
Wang Yabo,
Wang Xingyu,
Le Bitoux MarieAude,
Wagnieres Georges,
Vandenbergh Hubert,
Gonzalez Michel,
Ris HansBeat,
Perentes Jean Y,
Krueger Thorsten
Publication year - 2015
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.22329
Subject(s) - photodynamic therapy , mesothelioma , bioluminescence imaging , medicine , in vivo , chemotherapy , distribution (mathematics) , pathology , cancer research , chemistry , luciferase , biology , mathematical analysis , transfection , biochemistry , microbiology and biotechnology , organic chemistry , mathematics , gene
Background The pre‐conditioning of tumor vessels by low‐dose photodynamic therapy (L‐PDT) was shown to enhance the distribution of chemotherapy in different tumor types. However, how light dose affects drug distribution and tumor response is unknown. Here we determined the effect of L‐PDT fluence on vascular transport in human mesothelioma xenografts. The best L‐PDT conditions regarding drug transport were then combined with Lipoplatin ® to determine tumor response. in vivo . Lasers Surg. Med. 47:323–330, 2015. © 2015 Wiley Periodicals, Inc. Methods Nude mice bearing dorsal skinfold chambers were implanted with H‐Meso1 cells. Tumors were treated by Visudyne ® ‐mediated photodynamic therapy with 100 mW/cm 2 fluence rate and a variable fluence (5, 10, 30, and 50 J/cm 2 ). FITC‐Dextran (FITC‐D) distribution was assessed in real time in tumor and normal tissues. Tumor response was then determined with best L‐PDT conditions combined to Lipoplatin ® and compared to controls in luciferase expressing H‐Meso1 tumors by size and whole body bioluminescence assessment (n = 7/group). Results Tumor uptake of FITC‐D following L‐PDT was significantly enhanced by 10‐fold in the 10 J/cm 2 but not in the 5, 30, and 50 J/cm 2 groups compared to controls. Normal surrounding tissue uptake of FITC‐D following L‐PDT was significantly enhanced in the 30 J/cm 2 and 50 J/cm 2 groups compared to controls. Altogether, the FITC‐D tumor to normal tissue ratio was significantly higher in the 10 J/cm 2 group compared others. Tumor growth was significantly delayed in animals treated by 10 J/cm2‐L‐PDT combined to Lipoplatin ® compared to controls. Conclusions Fluence of L‐PDT is critical for the optimal distribution and effect of subsequently administered chemotherapy. These findings have an importance for the clinical translation of the vascular L‐PDT concept in the clinics. Lasers Surg. Med. 47:323–330, 2015. © 2015 Wiley Periodicals, Inc.