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7 October 2010 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
Veerle F. Casneuf, Louke Delrue, Nancy Van Damme, Pieter Demetter, Philippe Robert, Claire Corot, Philippe Duyck, Wim Ceelen, Tom Boterberg, Marc Peeters
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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.

Veerle F. Casneuf, Louke Delrue, Nancy Van Damme, Pieter Demetter, Philippe Robert, Claire Corot, Philippe Duyck, Wim Ceelen, Tom Boterberg, and Marc Peeters "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," Radiation Research 175(1), 10-20, (7 October 2010). https://doi.org/10.1667/RR2068.1
Received: 4 November 2009; Accepted: 1 July 2010; Published: 7 October 2010
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