Light Dosimetry for Intraperitoneal Photodynamic Therapy in a Murine Xenograft Model of Human Epithelial Ovarian Carcinoma
Lothar Lilge1, Kelly Molpus2, Tayyaba Hasan2 and Brian C. Wilson1
1Ontario Cancer Institute/Princess Margaret Hospital, Department of Medical Biophysics, University of Toronto, and Photonics Research Ontario 610 University Avenue, Toronto, Ontario, M5G 2M9, Canada. 2Wellman Laboratories of Photomedicine, Massachusetts General Hospital, 50 Blossom Street, Boston, Massachusetts, 02114, USA.
Background and Objective: Few studies have been published to date measuring spatially resolved fluence-rates in complex tissue geometries. Here we investigated three different intraperitoneal light delivery geometries in a murine ovarian cancer model by measuring the resultant light distributions and the resulting photodynamic response.
Materials and Methods: In vivo fluence-rate measurements mapping the light intensity in three transverse planes in the peritoneal cavity of mice were performed using fiber-optical detectors. Three different source fiber designs and placements were tested for their ability to provide uniform irradiation of the peritoneal cavity. The biological response to photodynamic therapy (PDT) consisting of three applications administered at 72 hr intervals, each consisting of 0.25 mg kg i.p. injection of Benzoporphyrin derivative-mono acid ring A, followed 90 minutes later by delivery of 15 J of 690 nm light. The tissue response was evaluated by measuring the number of remaining visible lesions and the total residual tumor mass.
Results: Fluence-rate measurements showed large variations in the fluence-rate distribution for similar intended treatments. The most uniform and reproducible illumination of the peritoneal cavity was achieved using two 18 mm long cylindrical emitting optical fibers for light delivery. Biological response was comparable when using a cut-end optical fiber illuminating the four quadrants of the abdomen sequentially, or two 18 mm long diffusing fibers. No correlation was found between fluence-rate distribution measured in one population of animals and the biological response in a separate set of similarly treated animals.
Conclusions: Representative fluence-rate distribution mapping in complex tissue geometries is of limited value to an individual PDT treatment, but may be useful in testing new illumination schemes. For actual PDT in complex tissue geometries, volume surveillance of the fluence rate during treatment may be required for acceptable dosimetry. In this particular model, a larger number of extended sources is required to increase uniformity of the illumination to reduce unwanted cytotoxic side effects. Subsequent increase of the total delivered energy to the tumor may be possible.