• John T Pierce, Steve S Cho, Shayoni Nag, Ryan Zeh, Jun Jeon, David Holt, Amy Durham, MacLean P Nasrallah, Sunil Singhal, and Lee John Y K JYK Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania..
• Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
• Neurosurgery. 2019 Sep 1; 85 (3): 359-368.

BackgroundMeningiomas are well-encapsulated benign brain tumors and surgical resection is often curative. Nevertheless, this is not always possible due to the difficulty of identifying residual disease intraoperatively. We hypothesized that meningiomas overexpress folate receptor alpha (FRα), allowing intraoperative molecular imaging by targeting FRα with a near-infrared (NIR) dye.ObjectiveTo determine FRα expression in both human and canine meningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging.MethodsTissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FRα along with normal dura, skeletal muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma and tuberculum sella meningioma in a clinical trial in which the patient received an infusion of folate-linked, NIR fluorescent dye prior to surgery.ResultsIn the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and 50% of grade III tumors overexpressed FRα. In the 7 canine meningioma samples, 100% stained positively for FRα. Both human and canine normal dura from autopsy samples demonstrated no evidence of FRα overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FRα immunohistochemistry staining.ConclusionThis study directly demonstrates FRα overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.Copyright © 2018 by the Congress of Neurological Surgeons.

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