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  • Folate Receptor Overexpression in Human and Canine Meningiomas – Immunohistochemistry and Case Report of Intraoperative Molecular Imaging

    Final Number:

    Steve Cho; John Thomas Pierce MS; Sunil Singhal; John Y.K. Lee MD

    Study Design:

    Subject Category:

    Meeting: Congress of Neurological Surgeons 2018 Annual Meeting - Late Breaking Science

    Introduction: Meningiomas are well-encapsulated benign brain tumors and surgical resection is often curative, especially for the low-grade meningiomas. Nevertheless, this is not always possible due to the difficulty of identifying residual disease intraoperatively and recurrences are common. Intraoperative near-infrared imaging has demonstrated utility in real-time, highly sensitive detection of residual neoplasm. We hypothesized that meningiomas would overexpress folate-receptor-alpha (FRa), allowing targeted intraoperative molecular imaging with a folate-linked near-infrared dye. In this study, we sought to determine FRa expression in both human and canine meningioma specimens. We also present a case study of a meningioma resection with intraoperative near-infrared fluorescence imaging, as a proof-of-concept for this novel technique.

    Methods: Tissue samples from 27 human meningioma and 7 canine meningioma were immunohistochemically stained for FRa, with normal dura, skeletal muscle, and kidney tissue serving as the controls. We then enrolled a patient with a concurrent pituitary adenoma and tuberculum-sella meningioma in a clinical trial, in which the patient received an infusion of folate-linked, near-infrared fluorescent dye prior to surgery.

    Results: In the cohort of human meningiomas, 9 WHO Grade I, 12 Grade II, and 6 Grade III tumors were identified. 89% of WHO Grade I, 67% of Grade II, and 50% of Grade III tumors overexpressed FRa. All 7 canine meningioma samples stained positively for FRa. Normal dura from both human and canine autopsy samples demonstrated no evidence of FRa overexpression. In the case study, the meningioma demonstrated a high near-infrared signal-to-background-ratio of 4.0 and demonstrated strong FRa immunohistochemistry staining. Near-infrared imaging detected an area of residual neoplasm, which had been previously missed.

    Conclusions: This study directly demonstrates FRa overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRa-targeting near-infrared dye. Thus, meningiomas are suitable for tumor-specific molecular imaging, which could improve resection rates and patient outcomes.

    Patient Care: Tissue-specific near-infrared imaging has definite benefits over non-specific imaging currently being studied. We demonstrate here that the folate receptor is an excellent potential candidate for tumor-targeted intraoperative imaging. Such imaging techniques can sensitively and specifically delineate residual tumor after resection, potentially enhancing resection rates and improving patient outcome/survival.

    Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of near-infrared imaging in potentially enhancing resection rates in intracranial tumors 2) Discuss the role of targeted molecular imaging in neurosurgery


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