Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17
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Quirijn R.J.G. Tummers1,5,*, Charlotte E.S. Hoogstins1,5,*, Katja N. Gaarenstroom2, Cor D. de Kroon2, Mariette I.E. van Poelgeest2, Jaap Vuyk3, Tjalling Bosse4, Vincent T.H.B.M Smit4, Cornelis J.H. van de Velde1, Adam F. Cohen5, Philip S. Low6, Jacobus Burggraaf5, Alexander L. Vahrmeijer1
1Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands
2Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands
3Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands
4Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands
5Centre for Human Drug Research, Leiden, The Netherlands
6Department of Chemistry, Purdue University, West Lafayette, IN, USA
*These authors have contributed equally to this work and share first authorship
Alexander L. Vahrmeijer, email: [email protected]
Keywords: image-guided surgery, fluorescence, folate-receptor alpha, breast cancer, ovarian cancer
Received: November 04, 2015 Accepted: February 11, 2016 Published: March 22, 2016
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.
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