title: Fluorescent-tilmanocept for tumor margin analysis in the mouse model.
abstract: BACKGROUND
  Dendritic cells (DC) are localized in close proximity to cancer cells in many well-known tumors, and thus maybe a useful target for tumor margin assessment.
  
  
  METHODS
  [(99m)Tc]- cyanine 7 (Cy7)-tilmanocept was synthesized and in vitro binding assays to bone marrow-derived DC were performed. Fifteen mice, implanted with either 4T1 mouse mammary or K1735 mouse melanoma tumors, were administered 1.0 nmol of [(99m)Tc]-Cy7-tilmanocept via tail vein injection. After fluorescence imaging 1 or 2 h after injection, the tumor, muscle, and blood were assayed for radioactivity to calculate percent-injected dose. Digital images of the tumors after immunohistochemical staining for DC were analyzed to determine DC density.
  
  
  RESULTS
  In vitro binding demonstrated subnanomolar affinity of [(99m)Tc]-Cy7-tilmanocept to DC (KA = 0.31 ± 0.11 nM). After administration of [(99m)Tc]-Cy7-tilmanocept, fluorescence imaging showed a 5.5-fold increase in tumor signal as compared with preinjection images and a 3.3-fold difference in fluorescence activity when comparing the tumor with the surgical bed after tumor excision. Immunohistochemical staining analysis demonstrated that DC density positively correlated with tumor percent of injected dose per gram (r = 0.672, P = 0.03), and higher DC density was observed at the periphery versus center of the tumor (186 ± 54 K versus 64 ± 16 K arbitrary units, P = 0.001).
  
  
  CONCLUSIONS
  [(99m)Tc]-Cy7-tilmanocept exhibits in vitro and in vivo tumor-specific binding to DC and maybe useful as a tumor margin targeting agent.
authors.affiliation: Department of Surgery, University of San Diego, California.
authors.forename: Ava
authors.initials: A
authors.lastname: Hosseini
authors.affiliation: Department of Surgery, University of San Diego, California.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Baker
authors.affiliation: Department of Surgery, University of San Diego, California.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Tokin
authors.affiliation: Department of Radiology, University of San Diego, California; In Vivo Cancer and Molecular Imaging Center, University of San Diego, California.
authors.forename: Zhengtao
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Radiology, University of San Diego, California; In Vivo Cancer and Molecular Imaging Center, University of San Diego, California; Moores UCSD Cancer Center, University of San Diego, California.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hall
authors.affiliation: Moores UCSD Cancer Center, University of San Diego, California; Department of Reproductive Medicine, University of San Diego, California.
authors.forename: Dwayne G
authors.initials: DG
authors.lastname: Stupak
authors.affiliation: Moores UCSD Cancer Center, University of San Diego, California; Department of Reproductive Medicine, University of San Diego, California.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Surgery, University of San Diego, California; Moores UCSD Cancer Center, University of San Diego, California.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Wallace
authors.affiliation: Department of Radiology, University of San Diego, California; In Vivo Cancer and Molecular Imaging Center, University of San Diego, California; Moores UCSD Cancer Center, University of San Diego, California. Electronic address: dvera@ucsd.edu.
authors.forename: David R
authors.initials: DR
authors.lastname: Vera
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000737:chemistry; D039521:CD11c Antigen / Q000032:analysis / Q000737:chemistry; D002232:Carbocyanines / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000737:chemistry / Q000473:pathology*; D003911:Dextrans / Q000737:chemistry; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000473:pathology*; D008351:Mannans / Q000737:chemistry; D008546:Melanoma, Experimental / Q000737:chemistry / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008856:Microscopy, Fluorescence; D016284:Technetium Tc 99m Pentetate / Q000031:analogs & derivatives* / Q000737:chemistry; D014466:Ultraviolet Rays
chemical_list: D052160:Benzothiazoles; D039521:CD11c Antigen; D002232:Carbocyanines; D003911:Dextrans; D008351:Mannans; C431884:technetium-diethylenetriaminepentaacetic acid-mannosyl-dextran; C011204:cyanine dye 7; D016284:Technetium Tc 99m Pentetate
keywords: Dendritic cells; Fluorescence imaging; Lymphoseek; Tilmanocept; Tumor margins