Protoporphyrin IX fluorescence photobleaching is a useful tool to predict the response of rat ovarian cancer following hexaminolevulinate photodynamic therapy

Abstract

Accurate dosimetry was shown to be critical to achieve effective photodynamic therapy (PDT). This study aimed to assess the reliability of in vivo protoporphyrin IX (PpIX) fluorescence photobleaching as a predictive tool of the hexaminolevulinate PDT (HAL-PDT) response in a rat model of advanced ovarian cancer. Intraperitoneal 10(6) NuTu 19 cells were injected in 26 female rats Fisher 344. Peritoneal carcinomatosis was obtained 26 days post-tumor induction. Four hours post-intraperitoneal HAL (Photocure ASA, Oslo, Norway) injection, a laparoscopic procedure (D-light AutoFluorescence system, Karl Storz endoscope, Tuttlingen, Germany) and a fluorescence examination were made for 22 rats. The first group (LASER group, n=26) was illuminated with laser light using a 532 nm KTP laser (Laser Quantum, Stockport, UK) on 1 cm(2) surface at 45 J/cm(2). The second group (NO LASER group, n=26) served as controls. Biopsies were taken 24 hours after PDT. Semi-quantitative histology was performed and necrosis value was determined: 0--no necrosis to 4--full necrosis. Fluorescence was monitored before and after illumination on complete responders (NV=3-4; n=20) and non-responders (NV=0-2; n=6). High PpIX photobleaching corresponded with complete responders whereas low photobleaching corresponded with non-responders (P<0.05). A direct linear correlation was shown between photobleaching and necrosis (R(2)=0.89). In vivo PpIX fluorescence photobleaching is useful to predict the tissue response to HAL-PDT.