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Quantitative T2* imaging of metastatic human breast cancer to brain in the nude rat at 3 T.

Abstract
This study uses quantitative T(2)* imaging to track ferumoxides--protamine sulfate (FEPro)-labeled MDA-MB-231BR-Luc (231BRL) human breast cancer cells that metastasize to the nude rat brain. Four cohorts of nude rats were injected intracardially with FEPro-labeled, unlabeled or tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)-treated (to induce apoptosis) 231BRL cells, or saline, in order to develop metastatic breast cancer in the brain. The heads of the rats were imaged serially over 3-4 weeks using gradient multi-echo and turbo spin-echo pulse sequences at 3 T with a solenoid receive-only 4-cm-diameter coil. Quantitative T(2)* maps of the whole brain were obtained by the application of single-exponential fitting to the signal intensity of T(2)* images, and the distribution of T(2)* values in brain voxels was calculated. MRI findings were correlated with Prussian blue staining and immunohistochemical staining for iron in breast cancer and macrophages. Quantitative analysis of T(2)* from brain voxels demonstrated a significant shift to lower values following the intracardiac injection of FEPro-labeled 231BRL cells, relative to animals receiving unlabeled cells, apoptotic cells or saline. Quartile analysis based on the T(2)* distribution obtained from brain voxels demonstrated significant differences (p < 0.0083) in the number of voxels with T(2)* values in the ranges 10-35  ms (Q1), 36-60  ms (Q2) and 61-86  ms (Q3) from 1 day to 3 weeks post-infusion of labeled 231BRL cells, compared with baseline scans. There were no significant differences in the distribution of T(2)* obtained from serial MRI in rats receiving unlabeled or TRAIL-treated cells or saline. Histologic analysis demonstrated isolated Prussian blue-positive breast cancer cells scattered in the brains of rats receiving labeled cells, relative to animals receiving unlabeled or apoptotic cells. Quantitative T(2)* analysis of FEPro-labeled metastasized cancer cells was possible even after the hypointense voxels were no longer visible on T(2)*-weighted images.
AuthorsHo-Taek Song, Elaine K Jordan, Bobbi K Lewis, Eric Gold, Wei Liu, Joseph A Frank
JournalNMR in biomedicine (NMR Biomed) Vol. 24 Issue 3 Pg. 325-34 (Apr 2011) ISSN: 1099-1492 [Electronic] England
PMID20949637 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
CopyrightThis article is a U.S. Government work and is in the public domain in the U.S.A. Published in 2010 by John Wiley & Sons, Ltd.
Chemical References
  • Dextrans
  • Magnetite Nanoparticles
  • Protamines
  • ferumoxides
Topics
  • Animals
  • Brain Neoplasms (pathology, secondary)
  • Breast Neoplasms (pathology)
  • Cell Line, Tumor
  • Dextrans (metabolism)
  • Female
  • Humans
  • Magnetic Resonance Imaging (methods)
  • Magnetite Nanoparticles
  • Neoplasm Metastasis
  • Neoplasm Transplantation
  • Protamines (metabolism)
  • Rats
  • Rats, Nude

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