Continuous or fractionated photodynamic therapy? Comparison of three PDT schemes for ovarian peritoneal micrometastasis treatment in a rat model

Abstract

This experimental study aimed to compare three illumination schemes to optimize hexaminolaevulinate (HAL)-PDT in a rat tumor model with advanced ovarian cancer. Peritoneal carcinomatosis was induced by intraperitoneal 5×10(6)NuTu-19 cells injection in 60 female rats Fisher 344. Carcinomatosis was obtained 50 days post-tumor induction. Four hours post-intraperitoneal HAL (Photocure ASA, Oslo, Norway) injection, three different schemes of PDT were performed during 25 min on a 1cm(2) area. (A) Fractionated illumination (n=20) with an on-off cycle ("on": 2 min and "off": 1 min) at 30mW cm(-2) until a fluence of 30J cm(-2), (B) continuous illumination (n=20) at 30mW cm(-2) with a fluence of (45J cm(-2)C) continuous illumination (n=20) at 20mW cm(-2) with a fluence of 30J cm(-2). Laser light was generated using a 532nm KTP laser (Laser Quantum, Stockport, UK). Biopsies were taken 24h after treatment. Quantitative histology was performed. Necrosis value was determined: 0-no necrosis to 4-full necrosis. Depth of necrosis was then measured for each sample and correlated to Necrosis value. HAL-PDT was efficient in producing necrosis irrespective of the scheme. Tumor destruction was superior with fractionated illumination compared to both continuous illumination schemes regarding to the depth of necrosis (213±113μm vs 154±133μm vs 171±155μm) (p<0.05) or to the full necrosis rate (50% vs 30% vs 10%) (p<0.0001). Fractionated illumination during photodynamic therapy (PDT) was shown to improve tumor response. Fractionated illumination with short intervals should be considered for an effective PDT of advanced ovarian cancer.