title: A pre-targeting strategy for MR imaging of functional molecules using dendritic Gd-based contrast agents.
abstract: OBJECTIVE
  We aimed to establish a magnetic resonance imaging (MRI) protocol for the sensitive and specific imaging of functional molecules with a pre-targeting strategy utilizing the streptavidin-biotin interaction. Membrane type-1 matrix metalloproteinase (MT1-MMP) was selected as the target molecule.
  
  
  METHODS
  The biotinylated polyamidoamine dendrimer (PAMAM)-based contrast agent (Bt-PAMAM-DTPA(Gd)) was prepared, and its proton relaxivity (r1) and affinity to streptavidin were evaluated. Tumor-bearing mice were pre-targeted with streptavidin-conjugated anti-MT1-MMP monoclonal antibody (mAb), streptavidin-conjugated negative control IgG, or saline and 3 days later were injected with Bt-PAMAM-DTPA(Gd) followed immediately by MRI for a period of 3 h.
  
  
  RESULTS
  High r1 (15.5 L mmol(-1) s(-1)) and 1.9-fold higher affinity than D-biotin were obtained. Significantly higher relative tumor signals were observed in mice pre-targeted with streptavidin-conjugated anti-MT1-MMP mAb (165% at 3 h vs. pre-administration) than with saline or streptavidin-conjugated negative control IgG (P < 0.0001).
  
  
  CONCLUSIONS
  This pre-targeting approach can accomplish sensitive and specific in vivo MRI of functional molecules.
authors.affiliation: Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Sano
authors.forename: Takashi
authors.initials: T
authors.lastname: Temma
authors.forename: Takashi
authors.initials: T
authors.lastname: Azuma
authors.forename: Ryusuke
authors.initials: R
authors.lastname: Nakai
authors.forename: Michiko
authors.initials: M
authors.lastname: Narazaki
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kuge
authors.forename: Hideo
authors.initials: H
authors.lastname: Saji
mesh_terms: D000818:Animals; D019921:Biotinylation; D002850:Chromatography, Gel; D003287:Contrast Media; D050091:Dendrimers; D019786:Gadolinium DTPA; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D051379:Mice; D019047:Phantoms, Imaging; D019809:Streptavidin / Q000378:metabolism
chemical_list: D003287:Contrast Media; D050091:Dendrimers; D019809:Streptavidin; D053511:Matrix Metalloproteinase 14; D019786:Gadolinium DTPA