[Specific folic-acid targeted photosensitizer. The first step toward intraperitoneal photodynamic therapy for epithelial ovarian cancer].

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.