A Novel Tumor-Specific Agent for Intraoperative Near-Infrared Fluorescence Imaging: A Translational Study in Healthy Volunteers and Patients with Ovarian Cancer
- 14 June 2016
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Clinical Cancer Research
- Vol. 22 (12), 2929-2938
- https://doi.org/10.1158/1078-0432.ccr-15-2640
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. Clin Cancer Res; 22(12); 2929–38. ©2016 AACR.Keywords
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This publication has 36 references indexed in Scilit:
- The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancerCellular Oncology, 2011
- Neoadjuvant Chemotherapy or Primary Surgery in Stage IIIC or IV Ovarian CancerThe New England Journal of Medicine, 2010
- Folate Receptor β Is Expressed by Tumor-Associated Macrophages and Constitutes a Marker for M2 Anti-inflammatory/Regulatory MacrophagesCancer Research, 2009
- Imaging in the era of molecular oncologyNature, 2008
- Folate receptor alpha as a tumor target in epithelial ovarian cancerGynecologic Oncology, 2008
- Microenvironmental regulation of metastasisNature Reviews Cancer, 2008
- Fibroblast autofluorescence in connective tissue disorders: a future tool for clinical and differential diagnosis?Journal of Biomedical Optics, 2008
- Surgery for ovarian cancer: how to improve survivalThe Lancet, 2006
- Distinct Role of Macrophages in Different Tumor MicroenvironmentsCancer Research, 2006
- Complement activation-related pseudoallergy: A new class of drug-induced acute immune toxicityToxicology, 2005