Intraoperative fluorescence imaging of peritoneal dissemination of ovarian carcinomas. A preclinical study

ObjectiveImprovement of the management and outcome of ovarian cancers may require intraoperative detection and therapeutic intervention to treat minimal residual disease after complete surgery. The aim of this study was to validate the importance of fluorescence in the peroperative detection of human ovarian adenocarcinoma cells and to determine its efficiency in detecting infra millimetric tumor metastases.MethodsA fluorescent RAFT-(cRGD)4 tracer molecule (AngioStamp®) was used. The tracer is based on a biomarker, which has a very high affinity for the αvβ3 integrin, which is overexpressed in a large ratio of cancer cells and neovessel endothelial cells during angiogenesis. Infrared fluorescence was visualized with Fluobeam®, an open fluorescent imaging system that could potentially be used in peroperative conditions in the future.ResultsThis novel technique allowed the specific detection of residual tumor deposits and inframillimetric metastases, smaller than 500 μm, which were resected under fluorescent guidance. AngioStamp® was able to detect all types of cell lines, derived from human ovarian adenocarcinomas, before or after chemotherapy treatment in animals. The effectiveness of AngioStamp® for the detection of various human ovarian adenocarcinomas was assessed on 10 different fragments of tumor, implanted subcutaneously in nude mice. All implanted tumor fragments were visualized by AngioStamp®.ConclusionsThe high rate of recurrence after apparently complete surgery and/or complete clinical response to chemotherapy implies that most patients have undetected minimal residual disease. Novel techniques such as laparoscopic or laparotomic fluorescence may prove to be crucial in reassessing the definition of primary outcome in ovarian cancer management.

Research highlights
► Per-operative detection of infra-millimetric ovarian adenocarcinoma tumors.
► Targeting of the tumor cells was possible even after a chemotherapy treatment.
► Most patients could benefit from per-operative detection of ovarian cancer cells.