{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T07:06:28Z","timestamp":1786863988905,"version":"build-2736575974"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2018,8,3]],"date-time":"2018-08-03T00:00:00Z","timestamp":1533254400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA193556"],"award-info":[{"award-number":["R01 CA193556"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000003"],"award-info":[{"award-number":["UL1TR000003"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007929","name":"Institute for Translational Medicine and Therapeutics","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007929","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007928","name":"Perelman School of Medicine at the University of Pennsylvania","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007928","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurosurg.","NEUROS"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>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 (FR\u03b1), allowing intraoperative molecular imaging by targeting FR\u03b1 with a near-infrared (NIR) dye.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>To determine FR\u03b1 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Tissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FR\u03b1 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>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 FR\u03b1. In the 7 canine meningioma samples, 100% stained positively for FR\u03b1. Both human and canine normal dura from autopsy samples demonstrated no evidence of FR\u03b1 overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FR\u03b1 immunohistochemistry staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>This study directly demonstrates FR\u03b1 overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FR\u03b1-targeting dye.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/neuros\/nyy356","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T16:46:17Z","timestamp":1532105177000},"page":"359-368","source":"Crossref","is-referenced-by-count":10,"title":["Folate Receptor Overexpression in Human and Canine Meningiomas\u2014Immunohistochemistry and Case Report of Intraoperative Molecular Imaging"],"prefix":"10.1227","volume":"85","author":[{"given":"John T","family":"Pierce","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve S","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shayoni","family":"Nag","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Zeh","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jeon","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"},{"name":"Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Durham","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MacLean P","family":"Nasrallah","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Singhal","sequence":"additional","affiliation":[{"name":"Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Y K","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2019,9]]},"reference":[{"issue":"6","key":"bib1-20231011","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1227\/01.NEU.0000188281.91351.B9","article-title":"Epidemiology of intracranial meningioma","volume":"57","author":"Claus","year":"2005","journal-title":"Neurosurgery"},{"issue":"1","key":"bib2-20231011","doi-asserted-by":"crossref","first-page":"58","DOI":"10.3171\/jns.1986.64.1.0058","article-title":"Recurrence of intracranial meningiomas: the role played by regional multicentricity","volume":"64","author":"Borovich","year":"1986","journal-title":"J Neurosurg"},{"issue":"1","key":"bib3-20231011","doi-asserted-by":"crossref","first-page":"18","DOI":"10.3171\/jns.1985.62.1.0018","article-title":"Meningioma: analysis of recurrence and progression following neurosurgical resection","volume":"62","author":"Mirimanoff","year":"1985","journal-title":"J Neurosurg"},{"issue":"4","key":"bib4-20231011","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0360-3016(02)04356-0","article-title":"Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas","volume":"55","author":"Pollock","year":"2003","journal-title":"Int J Radiat Oncol Biol Phys"},{"issue":"1","key":"bib5-20231011","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1136\/jnnp.20.1.22","article-title":"The recurrence of intracranial meningiomas after surgical treatment","volume":"20","author":"Simpson","year":"1957","journal-title":"J Neurol Neurosurg Psychiat"},{"issue":"1","key":"bib6-20231011","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1227\/NEU.0000000000000117","article-title":"5-Aminolevulinic acid-induced protoporphyrin IX fluorescence in meningioma","volume":"10","author":"Valdes","year":"2014","journal-title":"Oper Neurosurg"},{"issue":"3 Suppl 1","key":"bib7-20231011","first-page":"102","article-title":"Usefulness of intraoperative photodynamic diagnosis using 5-Aminolevulinic acid for meningiomas with cranial invasion: technical case report","volume":"62","author":"Morofuji","year":"2008","journal-title":"Neurosurgery"},{"issue":"4","key":"bib8-20231011","doi-asserted-by":"crossref","first-page":"840","DOI":"10.3171\/2013.12.JNS131642","article-title":"Predictive value of intraoperative 5-aminolevulinic acid-induced fluorescence for detecting bone invasion in meningioma surgery","volume":"120","author":"Puppa","year":"2014","journal-title":"J Neurosurg"},{"issue":"6","key":"bib9-20231011","doi-asserted-by":"crossref","first-page":"899","DOI":"10.2967\/jnumed.107.049478","article-title":"Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors","volume":"49","author":"Fisher","year":"2008","journal-title":"J Nucl Med"},{"issue":"3","key":"bib10-20231011","first-page":"362","article-title":"Sorting of the human folate receptor in MDCK cells","volume":"37","author":"Kim","year":"2004","journal-title":"J Biochem Mol Biol"},{"issue":"1","key":"bib11-20231011","doi-asserted-by":"crossref","first-page":"506","DOI":"10.2741\/1815","article-title":"Role of folate receptor genes in reproduction and related cancers","volume":"11","author":"Elnakat","year":"2006","journal-title":"Front Biosci"},{"issue":"3","key":"bib12-20231011","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.ygyno.2007.11.020","article-title":"Folate receptor alpha as a tumor target in epithelial ovarian cancer","volume":"108","author":"Kalli","year":"2008","journal-title":"Gynecol Oncol"},{"issue":"2","key":"bib13-20231011","doi-asserted-by":"crossref","first-page":"187","DOI":"10.2460\/ajvr.75.2.187","article-title":"Assessment of folate receptor expression and folate uptake in multicentric lymphomas in dogs","volume":"75","author":"Childress","year":"2014","journal-title":"Am J Vet Res"},{"issue":"10","key":"bib14-20231011","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1038\/nm.2472","article-title":"Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-\u03b1 targeting: first in-human results","volume":"17","author":"Van Dam","year":"2011","journal-title":"Nat Med"},{"issue":"1","key":"bib15-20231011","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3171\/jns.1997.86.1.0113","article-title":"Progesterone and estrogen receptors in meningiomas: prognostic considerations","volume":"86","author":"Hsu","year":"1997","journal-title":"J Neurosurg"},{"issue":"9","key":"bib16-20231011","doi-asserted-by":"crossref","first-page":"2432","DOI":"10.1002\/1097-0142(19940501)73:9<2432::AID-CNCR2820730929>3.0.CO;2-S","article-title":"Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications","volume":"73","author":"Ross","year":"1994","journal-title":"Cancer"},{"issue":"S1","key":"bib17-20231011","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1038\/onc.2009.197","article-title":"Overview of molecular testing in non-small-cell lung cancer: mutational analysis, gene copy number, protein expression and other biomarkers of EGFR for the prediction of response to tyrosine kinase inhibitors","volume":"1","author":"John","year":"2009","journal-title":"Oncogene"},{"issue":"3","key":"bib18-20231011","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1007\/s11307-017-1054-1","article-title":"Optical surgical navigation for precision in tumor resections","volume":"19","author":"Harmsen","year":"2017","journal-title":"Mol Imaging Biol"},{"issue":"15","key":"bib19-20231011","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1212\/WNL.0000000000002020","article-title":"Body mass index, physical activity, and risk of adult meningioma and glioma","volume":"85","author":"Niedermaier","year":"2015","journal-title":"Neurology"},{"issue":"2","key":"bib20-20231011","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.ab.2004.12.026","article-title":"Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay","volume":"338","author":"Parker","year":"2005","journal-title":"Anal Biochem"},{"key":"bib21-20231011","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1146\/annurev.nu.16.070196.002441","article-title":"Folate receptors","volume":"16","author":"Antony","year":"1996","journal-title":"Annu Rev Nutr"},{"issue":"14","key":"bib22-20231011","first-page":"4218","article-title":"Differential expression of folate receptor in pituitary adenomas","volume":"63","author":"Evans","year":"2003","journal-title":"Cancer Res"},{"key":"bib23-20231011","article-title":"Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging","author":"Lee","journal-title":"J Neurosurg"},{"key":"bib1a-20231011","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3389\/fsurg.2016.00055","article-title":"Intraoperative fluorescence imaging for personalized brain tumor resection: current state and future directions","volume":"3","author":"Belykh","year":"2016","journal-title":"Front Surg"},{"key":"bib2a-20231011","doi-asserted-by":"crossref","first-page":"70","DOI":"10.4103\/2152-7806.72247","article-title":"Use of sodium fluorescein in skull base tumors","volume":"1","author":"da Silva","year":"2010","journal-title":"Surg Neurol Int"},{"issue":"6","key":"bib3a-20231011","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1002\/cncr.30419","article-title":"Intraoperative near-infrared fluorescence imaging targeting folate receptors identifies lung cancer in a large-animal model","volume":"123","author":"Keating","year":"2017","journal-title":"Cancer"},{"issue":"1","key":"bib4a-20231011","doi-asserted-by":"crossref","first-page":"791","DOI":"10.18632\/oncotarget.23155","article-title":"Folate receptor-alpha targeted near-infrared fluorescence imaging in high-risk endometrial cancer patients: a tissue microarray and clinical feasibility study","volume":"9","author":"Boogerd","year":"2018","journal-title":"Oncotarget"},{"issue":"sup1","key":"bib5a-20231011","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1080\/24699322.2017.1389410","article-title":"In vivo MR imaging of folate-receptor expression with the folate-specific nanospheres in a C6 glioblastoma model","volume":"22","author":"An","year":"2017","journal-title":"Comput Assist Surg (Abingdon)"},{"key":"bib6a-20231011","first-page":"1","article-title":"Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging","author":"Lee","year":"2017","journal-title":"J Neurosurg"}],"container-title":["Neurosurgery"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/neurosurgery\/article-pdf\/85\/3\/359\/31493284\/nyy356.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/www.ovid.com\/10.1093\/neuros\/nyy356","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:44:27Z","timestamp":1786121067000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1093\/neuros\/nyy356"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,3]]},"references-count":29,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1093\/neuros\/nyy356","relation":{},"ISSN":["0148-396X","1524-4040"],"issn-type":[{"value":"0148-396X","type":"print"},{"value":"1524-4040","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,3]]}}}