Evaluation of a fibrin-binding gadolinium chelate peptide tetramer in a brain glioma model

Invest Radiol. 2011 Mar;46(3):169-77. doi: 10.1097/RLI.0b013e3181f7a0b0.

Abstract

Purpose: 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.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Animals
  • Area Under Curve
  • Brain Neoplasms / pathology*
  • Contrast Media*
  • Disease Models, Animal
  • Fibrin / drug effects*
  • Fluorescent Antibody Technique, Direct
  • Gadolinium DTPA*
  • Glioma / pathology*
  • Heterocyclic Compounds*
  • Organometallic Compounds*
  • Rats
  • Rats, Inbred F344

Substances

  • Contrast Media
  • Heterocyclic Compounds
  • Organometallic Compounds
  • Fibrin
  • gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
  • Gadolinium DTPA