Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17

INTRODUCTION: Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. Feasibility of EC17, a FRα-targeting agent that fluoresces at 500nm, was demonstrated in a limited series of ovarian cancer patients. Our objective was to evaluate EC17 in a larger group of ovarian cancer patients. In addition, we assessed the feasibility of EC17 in patients with breast cancer. METHODS: Two-to-three hours before surgery 0.1mg/kg EC17 was intravenously administered to 12 patients undergoing surgery for ovarian cancer and to 3 patients undergoing surgery for biopsy-proven FRα-positive breast cancer. The number of lesions/positive margins detected with fluorescence and concordance between fluorescence and tumor- and FRα-status was assessed in addition to safety and pharmacokinetics. RESULTS: Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology. Seven out of these 44 (16%) were not detected with inspection/palpation. Histopathology demonstrated concordance between fluorescence and FRα- and tumor status. Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal. At the 500nm wavelength, autofluorescence of normal breast tissue was present to such extent that it interfered with tumor identification. CONCLUSIONS: FRα is a favorable target for fluorescence-guided surgery as EC17 produced a clear fluorescent signal in ovarian and breast cancer tissue. This resulted in resection of ovarian cancer lesions that were otherwise not detected. Notwithstanding, autofluorescence caused false-positive lesions in ovarian cancer and difficulty in discriminating breast cancer-specific fluorescence from background signal. Optimization of the 500nm fluorophore, will minimize autofluorescence and further improve intraoperative tumor detection.