Lasers in Surgery and Medicine 2015 January 12 [Epub ahead of print] [Link]

Wang Y, Wang X, Le Bitoux MA, Wagnieres G, Vandenbergh H, Gonzalez M, Ris HB, Perentes JY, Krueger T.

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/cm2 fluence rate and a variable fluence (5, 10, 30, and 50 J/cm2 ). 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/cm2 but not in the 5, 30, and 50 J/cm2 groups compared to controls. Normal surrounding tissue uptake of FITC-D following L-PDT was significantly enhanced in the 30 J/cm2 and 50 J/cm2 groups compared to controls. Altogether, the FITC-D tumor to normal tissue ratio was significantly higher in the 10 J/cm2 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.