John T Pierce1, Steve S Cho1,2, Shayoni Nag1, Ryan Zeh1, Jun Jeon1,2, David Holt3, Amy Durham4, MacLean P Nasrallah5, Sunil Singhal6, John Y K Lee1. 1. Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Veterinary Medicine, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania. 4. Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania. 5. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. 6. Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
BACKGROUND: Meningiomas 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. OBJECTIVE: To 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. METHODS: Tissue 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. RESULTS: In 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. CONCLUSION: This 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.
BACKGROUND:Meningiomas 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. OBJECTIVE: To determine FRα expression in both human and caninemeningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging. METHODS: Tissue samples of 27 humanmeningioma specimens and 7 caninemeningioma 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. RESULTS: In the cohort of humanmeningiomas, 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 caninemeningioma 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. CONCLUSION: This study directly demonstrates FRα overexpression in both human and caninemeningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.
Authors: John Y K Lee; Steve S Cho; Ryan Zeh; John T Pierce; Maria Martinez-Lage; Nithin D Adappa; James N Palmer; Jason G Newman; Kim O Learned; Caitlin White; Julia Kharlip; Peter Snyder; Philip S Low; Sunil Singhal; M Sean Grady Journal: J Neurosurg Date: 2017-08-25 Impact factor: 5.115
Authors: Ronald E Fisher; Barry A Siegel; Steven L Edell; Nelson M Oyesiku; David E Morgenstern; Richard A Messmann; Robert J Amato Journal: J Nucl Med Date: 2008-05-15 Impact factor: 10.057
Authors: 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 Journal: Oncotarget Date: 2017-12-11