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

Leonora S.F. Boogerd, Charlotte E.S. Hoogstins, Katja N. Gaarenstroom, Cornelis D. de Kroon, Jogchum J. Beltman, Tjalling Bosse, Ellen Stelloo, Jaap Vuyk, Philip S. Low, Jacobus Burggraaf, Alexander L. Vahrmeijer

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Objective: 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. Results: 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, falsepositive fluorescence was identified in 17/50 non-metastatic LNs, caused by OTL-38 targeting of FRβ, expressed by tumor-associated activated macrophages. Conclusions: 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. Methods: 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.

Original languageEnglish (US)
Pages (from-to)791-801
Number of pages11
JournalOncotarget
Volume9
Issue number1
DOIs
StatePublished - 2018

Keywords

  • Biomarker
  • FRα
  • Targeting
  • Tumor-specific imaging

ASJC Scopus subject areas

  • Oncology

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