A novel tumor-specific agent for intraoperative near-infrared fluorescence imaging: A translational study in healthy volunteers and patients with ovarian cancer

Charlotte E.S. Hoogstins, Quirijn R.J.G. Tummers, Katja N. Gaarenstroom, Cor D. De Kroon, J. Baptist M.Z. Trimbos, Tjalling Bosse, Vincent T.H.B.M. Smit, Jaap Vuyk, Cornelis J.H. Van De Velde, Adam F. Cohen, Philip S. Low, Jacobus Burggraaf, Alexander L. Vahrmeijer

Research output: Contribution to journalArticle

118 Scopus citations

Abstract

Purpose: Completeness of cytoreductive surgery is a key prognostic factor for survival in patients with ovarian cancer. The ability to differentiate clearly between malignant and healthy tissue is essential for achieving complete cytoreduction. Using current approaches, this differentiation is often difficult and can lead to incomplete tumor removal. Near-infrared fluorescence imaging has the potential to improve the detection of malignant tissue during surgery, significantly improving outcome. Here, we report the use of OTL38, a near-infrared (796 nm) fluorescent agent, that binds folate receptor alpha, which is expressed in >90% of epithelial ovarian cancers. Experimental Design: We first performed a randomized, placebo-controlled study in 30 healthy volunteers. Four single increasing doses of OTL38 were delivered intravenously. At fixed times following drug delivery, tolerability and blood/skin pharmacokinetics were assessed. Next, using the results of the first 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 fluorescence 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 identified previously using inspection and/or palpation. Conclusions: This study demonstrates that performing real-time intraoperative near-infrared fluorescence imaging using a tumor-specific agent is feasible and potentially clinically beneficial.

Original languageEnglish (US)
Pages (from-to)2929-2938
Number of pages10
JournalClinical Cancer Research
Volume22
Issue number12
DOIs
StatePublished - Jun 15 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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