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

Casneuf, Veerle F.; Delrue, Louke; Van Damme, Nancy; Demetter, Pieter; Robert, Philippe; Corot, Claire; Duyck, Philippe; Ceelen, Wim; Boterberg, Tom; Peeters, Marc

doi:10.1667/RR2068.1

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

Casneuf, Veerle F.

Delrue, Louke

Van Damme, Nancy

Demetter, Pieter

Robert, Philippe

Corot, Claire

Duyck, Philippe

Ceelen, Wim

Boterberg, Tom

Peeters, Marc

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.

Language

English

Source (journal)

Radiation research. - New York, N.Y.

Publication

New York, N.Y. : 2011

ISSN

0033-7587

DOI

10.1667/RR2068.1

Volume/pages

175 :1 (2011) , p. 10-20