Photodiagnosis and photodynamic therapy · 2010
Continuous or fractionated photodynamic therapy? Comparison of three PDT schemes for ovarian peritoneal micrometastasis treatment in a rat model.
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Estevez Juan Pablo, Ascencio Manuel, Colin Pierre, Farine Marie Odile, Collinet Pierre, Mordon Serge
Аннотация
OBJECTIVE: This experimental study aimed to compare three illumination schemes to optimize hexaminolaevulinate (HAL)-PDT in a rat tumor model with advanced ovarian cancer.
MATERIALS AND METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.
MATERIALS AND METHODS: 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.
RESULTS: 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).
CONCLUSION: 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.