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

Quirijn R.J.G Tummers,Charlotte E.S Hoogstins,Vincent T.H.B.M Smit,Tjalling Bosse,Cor D De Kroon,Jacobus Burggraaf,Alexander L Vahrmeijer,Jaap Vuyk,Cornelis J.H Van De Velde,Philip S Low,Katja N Gaarenstroom,Mariette I.E Van Poelgeest,Adam F Cohen

doi:10.18632/oncotarget.8282

Quirijn R.J.G Tummers, Charlotte E.S Hoogstins + Show 11 more

Open Access

https://doi.org/10.18632/oncotarget.8282

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Abstract

IntroductionIntraoperative 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.MethodsTwo-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.ResultsFluorescence 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.ConclusionsFRα 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.

Highlights

Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery
Fluorescence imaging in ovarian cancer patients allowed detection of 57 lesions of which 44 (77%) appeared malignant on histopathology
Fluorescence imaging in breast cancer patients, allowed detection of tumor-specific fluorescence signal

Summary

Introduction

Intraoperative fluorescence imaging of the folate-receptor alpha (FRα) could support completeness of resection in cancer surgery. In ovarian cancer for example, clear intraoperative detection of metastatic lesions can improve staging procedures in early stage ovarian cancer (FIGO I and IIa), and facilitate complete or optimal cytoreductive surgery in advanced stage disease (FIGO IIb to IV). Both the prevention of positive margins in solid tumors and the performance of adequate staging and complete/optimal cytoreduction will improve individual patient outcome [4,5,6,7,8,9]. There is a clear unmet need for intraoperative modalities that can identify tumor tissue with high sensitivity and specificity

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