title: Evaluation of a fibrin-binding gadolinium chelate peptide tetramer in a brain glioma model.
abstract: OBJECTIVE
  To compare a fibrin-targeted, high relaxivity gadolinium tetramer, EP-2104R, in terms of magnitude of contrast enhancement (CE) and temporal time course, to a conventional extracellular gadolinium chelate, in a brain glioma model at 1.5-T magnetic resonance imaging.
  
  
  METHODS
  Six rats were evaluated, with each animal receiving (for separate studies) 0.05 mmol/kg gadopentetate dimeglumine (Gd DTPA or Magnevist) and 0.0125 mmol/kg of EP-2104R, with the 2 magnetic resonance examinations separated in each animal by 24 hours. The compound (EP-2104R) was synthesized using published methodology, being comprised of an 11 amino acid peptide derivatized at both the C- and N-termini with Gd-DOTA-like (Dotarem-like) moieties. T1-weighted scans were acquired precontrast and for 5 consecutive 2-minute intervals postcontrast, and subsequently at 15 and 20 minutes postcontrast.
  
  
  RESULTS
  Maximum tumor contrast-to-noise and CE both occurred at 1 minute versus at 5 minutes following administration of Gd DTPA versus EP-2104R, respectively. Utilizing an equivalent dose on a Gd ion per body weight basis, signal-to-noise, contrast-to-noise, and CE were greater for EP-2104R at all time points postcontrast, yielding overall statistically significantly greater levels of all 3 parameters with the latter. With EP-2104R, improvements in CE ranged between 87% and 391%, increasing at each measured time postcontrast with the exception of a slight decrease from 15 to 20 minutes postadministration. Histopathology confirmed, using immunofluorescence technique, abnormally increased fibrin within the tumor.
  
  
  CONCLUSIONS
  Statistically significantly greater brain tumor enhancement was noted with greater lesion enhancement at all observed time points postcontrast for EP-2104R utilizing an equivalent concentration to Gd DTPA on a per gadolinium ion basis. These findings together with the prolonged time course of enhancement suggest possible fibrin-binding and altered distribution kinetics.
authors.affiliation: Department of Radiology, Scott & White Clinic and Hospital, Texas A&M University Health Science Center, Temple, TX, USA. dr.john.morelli@gmail.com
authors.forename: John N
authors.initials: JN
authors.lastname: Morelli
authors.forename: Val M
authors.initials: VM
authors.lastname: Runge
authors.forename: Jonathon M
authors.initials: JM
authors.lastname: Williams
authors.forename: Robert S
authors.initials: RS
authors.lastname: Beissner
authors.forename: Michael
authors.initials: M
authors.lastname: Tweedle
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001932:Brain Neoplasms / Q000473:pathology*; D003287:Contrast Media; D004195:Disease Models, Animal; D005337:Fibrin / Q000187:drug effects*; D019085:Fluorescent Antibody Technique, Direct; D019786:Gadolinium DTPA; D005910:Glioma / Q000473:pathology*; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D005337:Fibrin; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D019786:Gadolinium DTPA