title: Fluence plays a critical role on the subsequent distribution of chemotherapy and tumor growth delay in murine mesothelioma xenografts pre-treated by photodynamic therapy.
abstract: 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.
  
  
  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.
authors: Department of Thoracic and Vascular Surgery, Centre Hospitalier Universitaire Vaudois, Ecole Polytechnique Federale de Lausanne, Lausanne, Switzerland.
authors: Yabo
authors: Y
authors: Wang
authors: Xingyu
authors: X
authors: Wang
authors: Marie-Aude
authors: MA
authors: Le Bitoux
authors: Georges
authors: G
authors: Wagnieres
authors: Hubert
authors: H
authors: Vandenbergh
authors: Michel
authors: M
authors: Gonzalez
authors: Hans-Beat
authors: HB
authors: Ris
authors: Jean Y
authors: JY
authors: Perentes
authors: Thorsten
authors: T
authors: Krueger
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D003911:Dextrans / Q000493:pharmacokinetics; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005456:Fluorescent Dyes / Q000493:pharmacokinetics; D006801:Humans; D008654:Mesothelioma / Q000473:pathology / Q000628:therapy*; D008819:Mice, Nude; D008853:Microscopy; D020360:Neoadjuvant Therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D011166:Porphyrins / Q000494:pharmacology; D000077362:Verteporfin; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011166:Porphyrins; C015219:fluorescein isothiocyanate dextran; C503131:lipoplatin; D000077362:Verteporfin; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin
keywords: drug/light conditions; mesothelioma lipoplatin®; photodynamic therapy; tumor response