Continuous or fractionated photodynamic therapy? Comparison of three PDT schemes for ovarian peritoneal micrometastasis treatment in a rat model.
OBJECTIVE
This experimental study aimed to compare three illumination schemes to optimize hexaminolaevulinate (HAL)-PDT in a rat tumor model with advanced ovarian cancer.


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).


CONCLUSIONS
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.
INSERM, U 703 - Univ. de Lille Nord de France - Lille University Hospital - CHRU, Lille, France.
Juan Pablo
JP
Estevez
Manuel
M
Ascencio
Pierre
P
Colin
Marie Odile
MO
Farine
Pierre
P
Collinet
Serge
S
Mordon
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000622:Aminolevulinic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid; C419924:5-aminolevulinic acid hexyl ester