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: Yabo Wang, Xingyu Wang, Marie-Aude Le Bitoux, Georges Wagnieres, Hubert Vandenbergh, Michel Gonzalez, Hans-Beat Ris, Jean Y Perentes, Thorsten Krueger
• Journal: Lasers in surgery and medicine (Lasers Surg Med) Vol. 47 Issue 4 Pg. 323-30 (Apr 2015) ISSN: 1096-9101 [Electronic] United States
• PMID: 25639847 (Publication Type: Journal Article)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Dextrans
• Fluorescent Dyes
• Photosensitizing Agents
• Porphyrins
• fluorescein isothiocyanate dextran
• lipoplatin
• Verteporfin
• Fluorescein-5-isothiocyanate
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Cell Line, Tumor
• Cisplatin (pharmacology)
• Dextrans (pharmacokinetics)
• Fluorescein-5-isothiocyanate (analogs & derivatives, pharmacokinetics)
• Fluorescent Dyes (pharmacokinetics)
• Humans
• Mesothelioma (pathology, therapy)
• Mice, Nude
• Microscopy
• Neoadjuvant Therapy
• Photochemotherapy
• Photosensitizing Agents (pharmacology)
• Porphyrins (pharmacology)
• Verteporfin
• Xenograft Model Antitumor Assays