title: Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors.
abstract: Primary brain tumors present significant challenges for surgical resection because of their location and the frequent occurrence of malignant projections extending beyond the primary tumor. Visualization of the tumor margins during surgery is critical for a favorable outcome. We report the use of IRDye 800CW chlorotoxin (CLTX) as a targeted imaging agent for brain tumors in a spontaneous mouse model of medulloblastoma, ND2:SmoA1. Specificity and functionality of the targeted agent were confirmed in cell-based assays. Tumors were detected by magnetic resonance imaging and IRDye 800CW CLTX administered to individual animals for optical imaging at 1-month increments. The integrity of the blood-brain barrier (BBB) was measured by Evan's Blue perfusion prior to sacrifice. Results show that IRDye 800CW CLTX specifically targeted tumor tissue. The extravasation of Evan's Blue was observed in all tumors, suggesting that the presence of the tumors can introduce alterations in the permeability of the BBB. Because increased vascular permeability was observed early in the disease model, larger dye-labeled imaging agents that exceed current BBB size restrictions may warrant renewed consideration as candidates for tumor detection and surgical resection. Our study provides data characterizing in vitro and in vivo use of IRDye 800CW CLTX as a broadly applicable tumor imaging agent.
authors.affiliation: Translational Research, LI-COR Biosciences, Lincoln, NE 68504, USA. joy.kovar@licor.com
authors.forename: Joy L
authors.initials: JL
authors.lastname: Kovar
authors.forename: Evan
authors.initials: E
authors.lastname: Curtis
authors.forename: Shadi F
authors.initials: SF
authors.lastname: Othman
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Simpson
authors.forename: D Michael
authors.initials: DM
authors.lastname: Olive
mesh_terms: D000818:Animals; D001557:Benzenesulfonates / Q000737:chemistry*; D001812:Blood-Brain Barrier / Q000378:metabolism; D045744:Cell Line, Tumor; D002528:Cerebellar Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008527:Medulloblastoma / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D012604:Scorpion Venoms / Q000737:chemistry* / Q000378:metabolism
chemical_list: D001557:Benzenesulfonates; C562366:IRDye 800CW; D007211:Indoles; D012604:Scorpion Venoms; C091539:Chlorotoxin; D020778:Matrix Metalloproteinase 2
keywords: Blood–brain barrier; Chlorotoxin; IRDye 800CW; In vivo imaging; Medulloblastoma; ND2:SmoA1 homozygous transgenic mouse