title: [Specific folic-acid targeted photosensitizer. The first step toward intraperitoneal photodynamic therapy for epithelial ovarian cancer].
abstract: OBJECTIVE
  Epithelial ovarian cancer (EOC) management remains association of debulking surgery in combination with platinum-based chemotherapy. Sixty percent of women with EOC considered in remission will develop recurrent disease. An option to improve the completion of cytoreductive surgery may be the use of photodynamic therapy to induce necrosis of peritoneal metastases. A limit of this technique was the toxicity induced by the lack of specificity of old-generation photosensitizer (PS) for tumor tissue if the light could not be specifically applied. To solve this problem, a solution is the design of selective PS. Folate receptor is a promising target for EOC targeted therapy. We present preclinical results concerning properties of a folic-acid targeted photosensitizer.
  
  
  METHODS
  Preclinical studies have been performed in vitro on murine and human cell lines of EOC and in vivo with a preclinical model of peritoneal carcinomatosis (Fisher F344 rat/NuTu-19 cell line). They aimed to precise the ability of PS to target specifically tumor tissue, to emit specific fluorescence, and to obtain cell death.
  
  
  RESULTS
  Tissue quantification of the PS showed specific incorporation of the folate-targeted PS within tumor tissue. Specificity for ovarian cancer metastases is better than previously reported with others photosensitizers (tumor-to-normal tissue ratio 9.6). We could detect specific fluorescence in vitro and in vivo on peritoneal metastases. Folic-acid targeted PDT allows to obtain human EOC cells death.
  
  
  CONCLUSIONS
  Specific PS may allow the development of efficient and safe intraperitoneal PDT procedure, which could play a role in the prevention of EOC peritoneal recurrences.
authors.affiliation: Service de chirurgie et cancérologie gynécologique et mammaire, Pitié-Salpêtrière, AP-HP, 75013 Paris, France; Inserm, U1189-ONCO THAI - Image Assisted Laser Therapy for Oncology, CHU de Lille, 59000 Lille, France. Electronic address: henriazais@gmail.com.
authors.forename: H
authors.initials: H
authors.lastname: Azaïs
authors.affiliation: UMR-CNRS 7274, laboratoire réactions et génie des procédés, Lorraine-université, 54001 Nancy cedex, France.
authors.forename: C
authors.initials: C
authors.lastname: Frochot
authors.affiliation: Service de gynécologie médicochirurgicale, CHRU de Lille, 59000 Lille, France; UMR 8161, CNRS, institut de biologie de Lille, institut Pasteur de Lille, université Lille-Nord de France, 59000 Lille, France.
authors.forename: A
authors.initials: A
authors.lastname: Grabarz
authors.affiliation: Inserm, U1189-ONCO THAI - Image Assisted Laser Therapy for Oncology, CHU de Lille, 59000 Lille, France; Service de gynécologie médicochirurgicale, CHRU de Lille, 59000 Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Khodja Bach
authors.affiliation: UMR-CNRS 7274, laboratoire réactions et génie des procédés, Lorraine-université, 54001 Nancy cedex, France.
authors.forename: L
authors.initials: L
authors.lastname: Colombeau
authors.affiliation: UMR 8161, CNRS, institut de biologie de Lille, institut Pasteur de Lille, université Lille-Nord de France, 59000 Lille, France.
authors.forename: N
authors.initials: N
authors.lastname: Delhem
authors.affiliation: Inserm, U1189-ONCO THAI - Image Assisted Laser Therapy for Oncology, CHU de Lille, 59000 Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Mordon
authors.affiliation: Inserm, U1189-ONCO THAI - Image Assisted Laser Therapy for Oncology, CHU de Lille, 59000 Lille, France; Service de gynécologie médicochirurgicale, CHRU de Lille, 59000 Lille, France.
authors.forename: P
authors.initials: P
authors.lastname: Collinet
mesh_terms: D000818:Animals; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D065426:Cytoreduction Surgical Procedures / Q000379:methods; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000187:drug effects; D005492:Folic Acid; D006801:Humans; D051379:Mice; D009336:Necrosis; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D058973:Folate Receptors, GPI-Anchored; D017319:Photosensitizing Agents; D005492:Folic Acid
keywords: Cancer de l’ovaire; Fluorescence; Folate receptor; Ovarian cancer; Photodynamic therapy; Photosensibilisateur; Photosensitizer; Récepteur au folate; Thérapie photodynamique