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.
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Authors | John N Morelli, Val M Runge, Jonathon M Williams, Robert S Beissner, Michael Tweedle |
Journal | Investigative radiology
(Invest Radiol)
Vol. 46
Issue 3
Pg. 169-77
(Mar 2011)
ISSN: 1536-0210 [Electronic] United States |
PMID | 21150792
(Publication Type: Comparative Study, Evaluation Study, Journal Article)
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Chemical References |
- Contrast Media
- Heterocyclic Compounds
- Organometallic Compounds
- Fibrin
- gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate
- Gadolinium DTPA
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Topics |
- 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
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