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

  • Oncotarget. 2016 May 31;7(22):32144-55. doi: 10.18632/oncotarget.8282.
Quirijn R J G Tummers  1  2 ,  Charlotte E S Hoogstins  1  2 ,  Katja N Gaarenstroom  3 ,  Cor D de Kroon  3 ,  Mariette I E van Poelgeest  3 ,  Jaap Vuyk  4 ,  Tjalling Bosse  5 ,  Vincent T H B M Smit  5 ,  Cornelis J H van de Velde  1 ,  Adam F Cohen  2 ,  Philip S Low  6 ,  Jacobus Burggraaf  2 ,  Alexander L Vahrmeijer  1
Affiliations
  • 1. Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
  • 2. Centre for Human Drug Research, Leiden, The Netherlands.
  • 3. Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
  • 4. Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
  • 5. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
  • 6. Department of Chemistry, Purdue University, West Lafayette, IN, USA.
PMID: 27014973 DOI: 10.18632/oncotarget.8282
Abstract

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.

Keywords
breast cancer; fluorescence; folate-receptor alpha; image-guided surgery; ovarian cancer.
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