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Oncotarget. 2017 Dec 11;9(1):791-801. doi: 10.18632/oncotarget.23155. eCollection 2018 Jan 2.

Folate receptor-α targeted near-infrared fluorescence imaging in high-risk endometrial cancer patients: a tissue microarray and clinical feasibility study.

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Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Chemistry and Center for Drug Discovery, Purdue University, West Lafayette, IN, USA.
Centre for Human Drug Research, Leiden, The Netherlands.
Leiden Academic Center for Drug Research, Leiden, The Netherlands.



Detection and resection of all malignant lesions is pivotal in staging and cytoreductive surgery (CRS) of endometrial cancer (EC). Intraoperative EC detection could be enhanced using OTL-38, a fluorescent-labelled folate receptor-α (FRα) targeted imaging agent. The objectives of this study were to investigate which subgroups of high-risk EC patients express FRα and assess feasibility of intraoperative EC detection using OTL-38.


FRα expression on TMA was significantly correlated with tumor type (p < 0.01). Eighty-two percent of serous and clear cell carcinomas showed FRα expression. Four patients were enrolled in the clinical study. Using fluorescence imaging all omental (n = 3) and lymph node (LN) metastases (n = 16) could be clearly identified, including one otherwise undetected omental metastasis. However, false-positive fluorescence was identified in 17/50 non-metastatic LNs, caused by OTL-38 targeting of FRβ, expressed by tumor-associated activated macrophages.


This study describes high FRα expression in serous and clear cell EC and demonstrates the first experience of intraoperative FRα-targeted tumor detection in patients with these subtypes of EC. Although all metastases could be clearly identified using OTL-38, the role of tumor-associated macrophages should be further evaluated.


Immunohistochemical (IHC) staining of FRα expression was performed on tissue micro arrays (TMA) of 116 patients with high-risk EC features. Patients with either serous or clear cell EC, planned for staging or CRS, were eligible for inclusion in the clinical study and received an intravenous dose of 0.0125 mg/kg OTL-38, 2-3 hours prior to surgery. Resected lesions, identified by standard-of-care and/or fluorescence imaging, were histopathologically assessed for FRα and tumor status.


FRα; biomarker; targeting; tumor-specific imaging

Conflict of interest statement

CONFLICTS OF INTEREST The Centre for Human Drug Research (a not-for-profit foundation) and the Leiden University Medical Center received financial compensation, study drug and equipment for the execution of this study from On Target Laboratories LLC.

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