title: Molecular imaging of fibrin in a breast cancer xenograft mouse model.
abstract: OBJECTIVE
  Fibrin deposition has been indicated within the stroma of a majority of solid tumors. Here we assess the feasibility of using the established fibrin-specific probe EP-2104R for noninvasive imaging of fibrin in the context of breast cancer.
  
  
  METHODS
  EP-2104R, untargeted gadopentetate dimeglumine (Gd-DTPA), and a newly synthesized nonfibrin binding control linear peptide (CLP) were compared using steady-state and dynamic contrast-enhanced magnetic resonance imaging in a breast cancer xenograft mouse model at 9.4 T.
  
  
  RESULTS
  EP-2104R transiently enhanced both tumor core and tumor periphery, but only the enhancement in the tumor periphery persisted even 90 minutes after EP-2104R administration. However, untargeted Gd-DTPA and CLP are not retained in the tumor periphery. The half-life of EP-2104R in the tumor periphery (103 ± 18 minutes) is significantly longer (P < 0.05) than that of either Gd-DTPA (29.6 ± 2.4 minutes) or CLP (42.4 ± 1.5 minutes), but the rate of clearance is similar for all the 3 probes from the tumor core. The presence of high concentrations of fibrin in the tumor periphery was corroborated using immunohistochemistry with a fibrin-specific antibody.
  
  
  CONCLUSIONS
  The persistent enhancement observed in the tumor periphery with EP-2104R is likely a result of its fibrin-specific binding rather than its size and demonstrates the feasibility of EP-2104R for molecular imaging of fibrin in tumor stroma.
authors.affiliation: Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ritika
authors.initials: R
authors.lastname: Uppal
authors.forename: Zdravka
authors.initials: Z
authors.lastname: Medarova
authors.forename: Christian T
authors.initials: CT
authors.lastname: Farrar
authors.forename: Guangping
authors.initials: G
authors.lastname: Dai
authors.forename: Anna
authors.initials: A
authors.lastname: Moore
authors.forename: Peter
authors.initials: P
authors.lastname: Caravan
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000473:pathology; D000818:Animals; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000473:pathology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005260:Female; D005337:Fibrin; D005682:Gadolinium; D019786:Gadolinium DTPA; D051379:Mice; D057054:Molecular Imaging; D010455:Peptides; D014183:Transplantation, Heterologous
chemical_list: C503783:EP-2104R; D010455:Peptides; D005337:Fibrin; D005682:Gadolinium; D019786:Gadolinium DTPA