Original Research

New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues

  1. Clemens C. Cyran MD1,2,
  2. Yanjun Fu PhD1,
  3. Hans-Juergen Raatschen MD1,3,
  4. Victor Rogut MD1,
  5. Bundit Chaopathomkul MD1,
  6. David M. Shames MD1,
  7. Michael F. Wendland PhD1,
  8. Benjamin M. Yeh MD1,
  9. Robert C. Brasch MD1,*

Article first published online: 24 JAN 2008

DOI: 10.1002/jmri.21245

Issue

Journal of Magnetic Resonance Imaging

Journal of Magnetic Resonance Imaging

Volume 27, Issue 3, pages 581–589, March 2008

Additional Information

How to Cite

Cyran, C. C., Fu, Y., Raatschen, H.-J., Rogut, V., Chaopathomkul, B., Shames, D. M., Wendland, M. F., Yeh, B. M. and Brasch, R. C. (2008), New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues. J. Magn. Reson. Imaging, 27: 581–589. doi: 10.1002/jmri.21245

Author Information

  1. 1

    Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California San Francisco, San Francisco, California

  2. 2

    Department of Clinical Radiology, University Hospital Munich - Grosshadern, Ludwig-Maximilians-University, Munich, Germany

  3. 3

    Klinik und Hochschulambulanz für Radiologie und Nuklearmedizin Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin, Berlin, Germany

*Center for Pharmaceutical and Molecular Imaging, Department of Radiology, University of California San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0628

Publication History

  1. Issue published online: 28 FEB 2008
  2. Article first published online: 24 JAN 2008
  3. Manuscript Accepted: 2 OCT 2007
  4. Manuscript Received: 22 JUL 2007

Funded by

  • NIH/NCI. Grant Numbers: R01 CA103850, CA082923

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article (HTML) Get PDF (401K)

Keywords:

  • dynamic contrast enhanced MRI;
  • macromolecular contrast media;
  • PEG-based contrast media;
  • tumor vascular leakiness;
  • cancer imaging characterization

Abstract

Purpose

To compare three new macromolecular polyethylene glycol (PEG) -core dendrimeric gadolinium(Gd)-based MRI contrast agents for their applicability in quantitative assays of endothelial leakiness and tissue vascular density for the differentiation of cancer from normal soft tissues.

Materials and Methods

Thirty-two athymic rats with human breast cancer xenografts (MDA-MB-435) were imaged by dynamic MRI following enhancement with one of three new (Gd-DOTA)-conjugated PEG-core dendrimer contrast agents (effective molecular weights 161 to 323 kDa). Results were compared with a prototype macromolecular contrast agent, albumin (Gd-DTPA). Assays of permeabilities (KPS; μL/min · 100 cm3) and tumor fractional plasma volumes (%) based on a two-compartment kinetic model were performed for skeletal muscle and tumors.

Results

The largest PEG-core contrast agent, PEG20,000-Gen4-(Gd-DOTA), leaked in breast tumors (KPS = 50 ± 23 μL/min · 100 cm3), while exhibiting no measurable transendothelial leak (KPS = 0 μL/min · 100 cm3) in normal soft tissue microvessels allowing successful differentiation (P < 0.05) of cancers from normal muscle. PEG12,000-Gen4-(Gd-DOTA) leaked in tumors and in normal muscle (KPS = 51 ± 26 and KPS = 21 ± 18μL/min · 100 cm3, respectively). The smallest agent, PEG12,000-Gen3-(Gd-DOTA) also showed a measurable leak in both normal and malignant microvessels.

Conclusion

MRI assays of vascular endothelial leakiness using new PEG-core, (Gd-DOTA)-conjugated macromolecular contrast agents proved applicable for the differentiation of human breast cancer from normal soft tissue. The apparent threshold in effective molecular weight for a clear differentiation of cancer from normal muscle with no measurable leak in the muscle is between 194 and 323 kDa. J. Magn. Reson. Imaging 2008. © 2008 Wiley-Liss, Inc.

View Full Article (HTML) Get PDF (401K)