TY - JOUR
T1 - Intraoperative imaging of folate receptor alpha positive ovarian and breast cancer using the tumor specific agent EC17
AU - Tummers, Quirijn R.J.G.
AU - Hoogstins, Charlotte E.S.
AU - Gaarenstroom, Katja N.
AU - de Kroon, Cor D.
AU - van Poelgeest, Mariette I.E.
AU - Vuyk, Jaap
AU - Bosse, Tjalling
AU - Smit, Vincent T.H.B.M.
AU - van de Velde, Cornelis J.H.
AU - Cohen, Adam F.
AU - Low, Philip S.
AU - Burggraaf, Jacobus
AU - Vahrmeijer, Alexander L.
PY - 2016/5/31
Y1 - 2016/5/31
N2 - 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.
AB - 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.
KW - Breast cancer
KW - Fluorescence
KW - Folate-receptor alpha
KW - Image-guided surgery
KW - Ovarian cancer
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U2 - 10.18632/oncotarget.8282
DO - 10.18632/oncotarget.8282
M3 - Article
C2 - 27014973
AN - SCOPUS:84973524616
SN - 1949-2553
VL - 7
SP - 32144
EP - 32155
JO - Oncotarget
JF - Oncotarget
IS - 22
ER -