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

SummaryObjectiveThis experimental study aimed to compare three illumination schemes to optimize hexaminolaevulinate (HAL)-PDT in a rat tumor model with advanced ovarian cancer.Materials and methodsPeritoneal carcinomatosis was induced by intraperitoneal 5 × 106 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 1 cm2 area. (A) Fractionated illumination (n = 20) with an on-off cycle (“on”: 2 min and “off”: 1 min) at 30 mW cm−2 until a fluence of 30 J cm−2, (B) continuous illumination (n = 20) at 30 mW cm−2 with a fluence of (45 J cm−2 C) continuous illumination (n = 20) at 20 mW cm−2 with a fluence of 30 J cm−2. Laser light was generated using a 532 nm KTP laser (Laser Quantum, Stockport, UK). Biopsies were taken 24 h 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.ResultsHAL-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 ± 113 μm vs 154 ± 133 μm vs 171 ± 155 μm) (p < 0.05) or to the full necrosis rate (50% vs 30% vs 10%) (p < 0.0001).ConclusionFractionated 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.