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.
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 K(trans) at MRI2 predicted its superior antivascular and antitumor effect at an early time. An increased K(trans) 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.
authors.affiliation: Department of Gastroenterology, Ghent University Hospital, De Pintelaan, Gent, Belgium. Veerle.Casneuf@UGent.be
authors.forename: Veerle F
authors.initials: VF
authors.lastname: Casneuf
authors.forename: Louke
authors.initials: L
authors.lastname: Delrue
authors.forename: Nancy
authors.initials: N
authors.lastname: Van Damme
authors.forename: Pieter
authors.initials: P
authors.lastname: Demetter
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Claire
authors.initials: C
authors.lastname: Corot
authors.forename: Philippe
authors.initials: P
authors.lastname: Duyck
authors.forename: Wim
authors.initials: W
authors.lastname: Ceelen
authors.forename: Tom
authors.initials: T
authors.lastname: Boterberg
authors.forename: Marc
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003287:Contrast Media; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D051379:Mice; D055806:Microvessels / Q000187:drug effects / Q000528:radiation effects; D009942:Organometallic Compounds; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000032:analysis / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D003287:Contrast Media; D009942:Organometallic Compounds; C531154:P846 compound; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor