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Evaluation of a Fibrin-Binding Gadolinium Chelate Peptide Tetramer in a Brain Glioma Model

Morelli, John N. MD*; Runge, Val M. MD; Williams, Jonathon M. MD*; Beissner, Robert S. MD, PhD; Tweedle, Michael PhD§

doi: 10.1097/RLI.0b013e3181f7a0b0
Original Article

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.

From the *Department of Radiology, Scott & White Clinic and Hospital, Texas A&M University Health Science Center, Temple, TX; †Department of Radiology, University of Texas Medical Branch, Galveston, TX; ‡Department of Pathology, Scott & White Clinic and Hospital, Texas A&M University Health Science Center, Temple, TX; and §Department of Radiology, The Ohio State University, Columbus, OH.

Received October 31, 2009; accepted for publication (after revision) August 9, 2010.

Reprints: John N. Morelli, MD, 2401 S. 31st Street, Temple, TX 76508. E-mail:

© 2011 Lippincott Williams & Wilkins, Inc.