title: 99mTc-labeled tricarbonyl his-CNA35 as an imaging agent for the detection of tumor vasculature.
abstract: Given the importance of angiogenesis for a tumor's survival and growth, several therapeutic strategies rely on the selective inhibition of angiogenesis and the destruction of existing tumor vasculature. These strategies raise the need for a noninvasive tool to evaluate tumor vasculature. We describe the radiosynthesis and evaluation of an imaging tracer that specifically binds tumor subendothelial collagen and thereby images tumor vasculature.
  
  
  METHODS
  (99m)Tc-tricarbonyl was prepared and labeled with His-collagen-binding adhesion protein 35 (CNA35). After in vitro specificity testing, in vivo biodistribution and dosimetric studies were performed in healthy nude mice via planar imaging. (99m)Tc-(CO)(3) His-CNA35 was evaluated for in vivo imaging of tumor vasculature in a HT29 colorectal carcinoma xenograft.
  
  
  RESULTS
  The labeling procedure yielded a compound with 95%-99% radiochemical purity and good in vitro stability. An in vitro binding test confirmed specificity and functionality. (99m)Tc-(CO)(3) His-CNA35 rapidly cleared from the blood and predominantly accumulated in the kidneys and liver. The effective dose for a proposed single injection of 500 MBq of (99m)Tc-(CO)(3) His-CNA35 is 3.70 mSv per organ or 2.01 mSv/g of tissue. Tumors were successfully visualized, and uptake correlated with ex vivo immunohistochemical staining of tumor vasculature.
  
  
  CONCLUSIONS
  (99m)Tc-(CO)(3) His-CNA35 may be a useful radioligand for the in vivo detection of tumor vasculature through subendothelial collagen binding. A noninvasive method of imaging tumor vasculature that could provide a reliable assessment of tumor vasculature would allow evaluation of the effectiveness of commonly used antiangiogenic therapies and determination of their optimal dosing and scheduling.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, The Netherlands.
authors.forename: Gilles
authors.initials: G
authors.lastname: Mees
authors.forename: Rudi
authors.initials: R
authors.lastname: Dierckx
authors.forename: Koen
authors.initials: K
authors.lastname: Mertens
authors.forename: Simon
authors.initials: S
authors.lastname: Vermeire
authors.forename: Magali
authors.initials: M
authors.lastname: Van Steenkiste
authors.forename: Chris
authors.initials: C
authors.lastname: Reutelingsperger
authors.forename: Yves
authors.initials: Y
authors.lastname: D'Asseler
authors.forename: Kathelijne
authors.initials: K
authors.lastname: Peremans
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Damme
authors.forename: Christophe
authors.initials: C
authors.lastname: Van de Wiele
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007150:Immunohistochemistry; D007553:Isotope Labeling; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000098:blood supply* / Q000000981:diagnostic imaging*; D009389:Neovascularization, Pathologic / Q000000981:diagnostic imaging*; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011874:Radiometry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D012039:Regional Blood Flow / Q000502:physiology; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D015815:Cell Adhesion Molecules; D015609:Organotechnetium Compounds; D019275:Radiopharmaceuticals; C571524:technetium 99m tricarbonyl His-CNA35