title: Tumor paint: a chlorotoxin:Cy5.5 bioconjugate for intraoperative visualization of cancer foci.
abstract: Toward the goal of developing an optical imaging contrast agent that will enable surgeons to intraoperatively distinguish cancer foci from adjacent normal tissue, we developed a chlorotoxin:Cy5.5 (CTX:Cy5.5) bioconjugate that emits near-IR fluorescent signal. The probe delineates malignant glioma, medulloblastoma, prostate cancer, intestinal cancer, and sarcoma from adjacent non-neoplastic tissue in mouse models. Metastatic cancer foci as small as a few hundred cells were detected in lymph channels. Specific binding to cancer cells is facilitated by matrix metalloproteinase-2 (MMP-2) as evidenced by reduction of CTX:Cy5.5 binding in vitro and in vivo by a pharmacologic blocker of MMP-2 and induction of CTX:Cy5.5 binding in MCF-7 cells following transfection with a plasmid encoding MMP-2. Mouse studies revealed that CTX:Cy5.5 has favorable biodistribution and toxicity profiles. These studies show that CTX:Cy5.5 has the potential to fundamentally improve intraoperative detection and resection of malignancies.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue N., Seattle, WA 98109, USA.
authors.forename: Mandana
authors.initials: M
authors.lastname: Veiseh
authors.forename: Patrik
authors.initials: P
authors.lastname: Gabikian
authors.forename: S-Bahram
authors.initials: SB
authors.lastname: Bahrami
authors.forename: Omid
authors.initials: O
authors.lastname: Veiseh
authors.forename: Miqin
authors.initials: M
authors.lastname: Zhang
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hackman
authors.forename: Ali C
authors.initials: AC
authors.lastname: Ravanpay
authors.forename: Mark R
authors.initials: MR
authors.lastname: Stroud
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kusuma
authors.forename: Stacey J
authors.initials: SJ
authors.lastname: Hansen
authors.forename: Deborah
authors.initials: D
authors.lastname: Kwok
authors.forename: Nina M
authors.initials: NM
authors.lastname: Munoz
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Sze
authors.forename: William M
authors.initials: WM
authors.lastname: Grady
authors.forename: Norman M
authors.initials: NM
authors.lastname: Greenberg
authors.forename: Richard G
authors.initials: RG
authors.lastname: Ellenbogen
authors.forename: James M
authors.initials: JM
authors.lastname: Olson
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism; D002232:Carbocyanines / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000737:chemistry; D005910:Glioma / Q000378:metabolism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence / Q000379:methods; D009369:Neoplasms / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D017785:Photons; D051381:Rats; D012604:Scorpion Venoms / Q000737:chemistry*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines; D005456:Fluorescent Dyes; D012604:Scorpion Venoms; C091539:Chlorotoxin; D020778:Matrix Metalloproteinase 2