Page 187 - Fluorescence-guided cancer surgery

permeability and reduced drainage. In the current study, several malignant lesions were identi ed using uorescence imaging. However, also 13 non- malignant lesions were uorescent, resulting in a false-positive ratio of 62%. This lack of speci city of the EPR e ect shows that it is not suitable for daily clinical practice. A more tumor-speci c accumulation pro le or ligand-binding mechanism could overcome this limitation.
Part 2: Clinical translation of innovative tumor-speci c uorescent contrast agents
Chapter 9 described the use of EC17, a folate analogue coupled to uorescein, for the identi cation of folate receptor alpha (FRα) positive ovarian and breast cancer. Intravenous administration of EC17, 2-3 hours before surgery, resulted in clear, bright uorescent metastatic lesions of ovarian cancer. It resulted in an increased resection of 16% more malignant lesions, and a 70% increase in detection of metastatic lesions on post-operative analyzed images. In breast cancer, the overexpression of FRα is lower than in ovarian cancer. Therefore, preoperative obtained biopsies were stained for receptor expression. This personalized approach guarantees that only patients that can potentially bene t from uorescence-guided surgery are included in trials using a tumor-speci c contrast agent. Also in breast cancer, a clear uorescent signal was seen in the tumor. Notwithstanding, auto uorescence signal of healthy tissue at 500nm caused false-positive lesions in breast cancer. In addition, this auto uorescence made it di cult to discriminate breast cancer-speci c uorescence from background uorescence. Imaging in the NIR uorescence light spectrum could solve this problem.
In chapter 10, we used a newly developed FRα speci c contrast agent. This agent, OTL38, consists of a folate analogue coupled to a NIR uorescent contrast agent ( uorescent at 800nm). First, tolerability and pharmacokinetics in blood and skin were assessed in a randomized, placebo-controlled, dose- ascending trial in healthy subjects. Hereafter three intravenous doses, selected based on the results from the healthy subject study, were administered to 12 patients with epithelial ovarian cancer, and scheduled for cytoreductive surgery. Clear accumulation of OTL38 in FRα positive tumors and metastases was seen, leading to the resection of 29% additional malignant lesions that were not identi ed by inspection and palpation. Almost no background uorescence was seen.
Summary and future perspectives 185