Page 158 - Fluorescence-guided cancer surgery

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Chapter 10
ABSTRACT
Purpose: Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to di erentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this di erentiation is often di cult and can lead to incomplete tumor removal. Near-infrared uorescence imaging has the potential to improve the detection of malignant tissue during surgery, signi cantly improving outcome. Here, we report the use of OTL38, a near- infrared (796 nm) uorescent agent that binds folate receptor alpha, that is expressed in >90% of epithelial ovarian cancers.
Experimental design: We rst performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At xed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the rst study, three doses were selected and administered to 12 patients who had epithelial ovarian cancer and were scheduled for cytoreductive surgery. We measured tolerability and blood pharmacokinetics, as well as the ability to detect the tumor using intraoperative uorescence imaging.
Results: Intravenous infusion of OTL38 in 30 healthy volunteers yielded an optimal dosage range and time window for intraoperative imaging. In 12 patients with ovarian cancer, OTL38 accumulated in folate receptor alpha- positive tumors and metastases, enabling the surgeon to resect an additional 29% of malignant lesions that were not identi ed previously using inspection and/or palpation.
Conclusions: This study demonstrates that performing real-time intraoperative near-infrared uorescence imaging using a tumor-speci c agent is feasible and potentially clinically bene cial.