New macromolecular polymeric MRI contrast agents for application in the differentiation of cancer from benign soft tissues
Article first published online: 24 JAN 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Magnetic Resonance Imaging
Volume 27, Issue 3, pages 581–589, March 2008
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
- Issue published online: 28 FEB 2008
- Article first published online: 24 JAN 2008
- Manuscript Accepted: 2 OCT 2007
- Manuscript Received: 22 JUL 2007
- NIH/NCI. Grant Numbers: R01 CA103850, CA082923
- dynamic contrast enhanced MRI;
- macromolecular contrast media;
- PEG-based contrast media;
- tumor vascular leakiness;
- cancer imaging characterization
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.
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.
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.