Development of an in vivo ovarian cancer peritoneal carcinomatosis model for radioimmunotherapy testing.

Abstract

Currently, Ovarian Cancer (OC) is the most lethal gynecological malignancy. In most patients, it progresses without clinical signs or symptoms, leading to a late diagnosis when it has already spread in the peritoneal cavity as peritoneal carcinomatosis (PC). To date, OC PC management is based on cytoreductive surgery to remove the macroscopic disease, followed by chemotherapy. Many patients respond to this treatment, but disease recurs in 70-90% of them. Therefore, new therapeutic approaches are needed. The field of targeted radionuclide therapy (TRT) has witnessed considerable progress and several radiopharmaceuticals have been approved in the last decade. In TRT, radiolabeled molecules are injected to specifically recognize, irradiate, and kill tumor cells. TRT is a multisite radiotherapy that delivers dose to all malignant lesions. Therefore, TRT could be an alternative approach for OC PC because conventional external beam radiotherapy cannot be used at curative dose due to toxicity to healthy tissues. Here, we describe an OC PC model based on grafting human SK-OV-3 OC cells in the peritoneal cavity of immunodeficient mice. We also explain how to label trastuzumab with lutetium-177 to specifically target and irradiate SK-OV-3 cell nodules in these mice, and how to monitor the response to this TRT in vivo. With minor variations, the same technique can be conveniently applied to a variety of human (or mouse) tumors.