Henri Azaïs1, Caroline Schmitt2, Meryem Tardivel3, Olivier Kerdraon4, Aurélie Stallivieri5, Céline Frochot5, Nacim Betrouni6, Pierre Collinet7, Serge Mordon6. 1. Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, F-59000 Lille, France; Department of Gynecology, University of Lille, 59000 Lille, France. Electronic address: henriazais@gmail.com. 2. Centre Français des Porphyries, Assistance Publique - Hôpitaux de Paris, Hôpital Louis Mourier, Colombes, France and INSERM U1149, Paris Diderot University, 75018 Paris, France. 3. Plate-Forme D'imagerie Cellulaire BICEL - IFR 114, Pôle Recherche, University of Lille, 59000 Lille, France. 4. Centre de Biologie-Pathologie, University of Lille, 59000 Lille, France. 5. Laboratoire Réactions et Génie des Procédés, UMR 7274CNRS - University of Lorraine, France. 6. Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, F-59000 Lille, France. 7. Univ. Lille, Inserm, CHU Lille, U1189 - ONCO-THAI - Image Assisted Laser Therapy for Oncology, F-59000 Lille, France; Department of Gynecology, University of Lille, 59000 Lille, France.
Abstract
BACKGROUND: Ovarian cancer's prognosis remains dire after primary therapy. Recurrence rate is disappointingly high as 60% of women with epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis during surgery is necessary as they are the main predictive factors of recurrences. Folate Receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells and intraperitoneal photodynamic therapy (PDT) could be a solution in addition to macroscopic cytoreductive surgery to treat peritoneal micrometastasis. The aim of this preclinical study is to assess the specificity of a folate-targeted photosensitizer for ovarian peritoneal micrometastasis. METHODS: We used the NuTu-19 epithelial ovarian cancer cell line to induce peritoneal carcinomatosis in female Fischer 344 rats. Three groups of 6 rats were studied (Control (no photosensitizer)/Non-conjugated photosensitizer (Porph)/Folate-conjugated photosensitizer (Porph-s-FA)). Four hours after the administration of the photosensitizer, animals were sacrificed and intraperitoneal organs tissues were sampled. FRα tissue expression was evaluated by immunohistochemistry. Tissue incorporation of photosensitizers was assessed by confocal microscopy and tissue quantification. RESULTS: FRα is overexpressed in tumor, ovary, and liver whereas, peritoneum, colon, small intestine, and kidney do not express it. Cytoplasmic red endocytosis vesicles observed by confocal microscopy are well correlated to FRα tissue expression. Photosensitizer tissue quantification shows a mean tumor-to-normal tissue ratio of 9.6. CONCLUSION: We demonstrated that this new generation folate-targeted photosensitizer is specific of epithelial ovarian peritoneal metastasis and may allow the development of efficient and safe intraperitoneal PDT procedure.
BACKGROUND: Ovarian cancer's prognosis remains dire after primary therapy. Recurrence rate is disappointingly high as 60% of women with epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis during surgery is necessary as they are the main predictive factors of recurrences. Folate Receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells and intraperitoneal photodynamic therapy (PDT) could be a solution in addition to macroscopic cytoreductive surgery to treat peritoneal micrometastasis. The aim of this preclinical study is to assess the specificity of a folate-targeted photosensitizer for ovarian peritoneal micrometastasis. METHODS: We used the NuTu-19 epithelial ovarian cancer cell line to induce peritoneal carcinomatosis in female Fischer 344 rats. Three groups of 6 rats were studied (Control (no photosensitizer)/Non-conjugated photosensitizer (Porph)/Folate-conjugated photosensitizer (Porph-s-FA)). Four hours after the administration of the photosensitizer, animals were sacrificed and intraperitoneal organs tissues were sampled. FRα tissue expression was evaluated by immunohistochemistry. Tissue incorporation of photosensitizers was assessed by confocal microscopy and tissue quantification. RESULTS: FRα is overexpressed in tumor, ovary, and liver whereas, peritoneum, colon, small intestine, and kidney do not express it. Cytoplasmic red endocytosis vesicles observed by confocal microscopy are well correlated to FRα tissue expression. Photosensitizer tissue quantification shows a mean tumor-to-normal tissue ratio of 9.6. CONCLUSION: We demonstrated that this new generation folate-targeted photosensitizer is specific of epithelial ovarian peritoneal metastasis and may allow the development of efficient and safe intraperitoneal PDT procedure.
Authors: Shubhankar Nath; Mohammad Ahsan Saad; Michael Pigula; Joseph W R Swain; Tayyaba Hasan Journal: Cancers (Basel) Date: 2019-11-27 Impact factor: 6.639