Title
Noninvasive monitoring of therapy-induced microvascular changes in a pancreatic cancer model using dynamic contrast-enhanced magnetic resonance imaging with P846, a new low-diffusible gadolinium-based contrast agent
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
New York, N.Y. ,
Subject
Human medicine
Source (journal)
Radiation research. - New York, N.Y.
Volume/pages
175(2011) :1 , p. 10-20
ISSN
0033-7587
ISI
000285858800002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Abstract
A predictive technique in the management of patients with cancer could improve the therapeutic index by allowing better individualization of treatment. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive technique that can provide anatomical and physiological information on the tumor and its microenvironment. We studied the effect of chemotherapy (gemcitabine), anti-angiogenesis therapy (sunitinib) and radiotherapy on the kinetics of DCE-MRI parameters in a preclinical model of pancreatic cancer using P846, a new low-diffusible contrast agent. Mice underwent DCE-MRI before treatment (MRI1), after 1 week of treatment (MRI2), and after 1 additional week (MRI3). Combined treatment with radiotherapy and sunitinib had a synergistic effect on tumor growth. In radiotherapy/sunitinib-treated mice, a decrease in Ktrans at MRI2 predicted its superior antivascular and antitumor effect at an early time. An increased Ktrans at MRI2, as seen in gemcitabine- and gemcitabine/sunitinib-treated mice, reflects increased permeability for P846 and might predict a smaller therapeutic effect at this early time. This study shows that the kinetics of DCE-MRI parameters depends on the contrast agent used. P846 appears to be a promising low-diffusible agent to monitor therapeutic effects in this preclinical cancer model, but further studies are needed to compare its behavior with Gd-DTPA and macromolecular-weight contrast agents. Sunitinib as a radiosensitizer is promising for future clinical trials in human pancreatic cancer.
E-info
https://repository.uantwerpen.be/docman/iruaauth/32c71c/8846eba7eb0.pdf
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