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Examining the acute effects of cediranib (RECENTINTM, AZD2171) treatment in tumor models: a dynamic contrast enhanced MRI (DCE-MRI) study using gadopentate

Lookup NU author(s): Professor Steve Wedge

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Abstract

Cediranib (RECENTIN, AZD2171) is a highly potent inhibitor of the tyrosine kinase activity associated with all three vascular endothelial growth factor (VEGF) receptors and is currently in Phase II/III clinical trials. Preclinically, cediranib inhibits VEGF signaling and angiogenesis in vivo and impedes solid tumor growth significantly. Clinically, changes observed using dynamic contrast-enhanced MRI (DCE-MRI) with gadopentate suggest that acute cediranib treatment compromises tumor hemodynamics. In this study, a DCE-MRI baseline scan using gadopentate was performed in nude rats bearing Lovo (human colorectal carcinoma) or C6 (rat glioma) tumors. Cediranib (3 mg/kg per day) or vehicle was then dosed orally (2, 26 and 50 h after the baseline scan; 12 rats per group) and a second scan acquired 2 h after the final dosing event. Mean values for K(trans) (Tofts and Kermode-derived) [Magn Reson Med 17 (1991) 357-67] and the initial area under the gadolinium concentration curve over the first 60 s (iAUC) were reduced significantly following cediranib treatment: K(trans) by 33% (P<.05) in both tumor models and iAUC by 23% (P>.05) and 33% (P>.005) in Lovo and C6, respectively. This is the first preclinical investigation to examine the effect of cediranib treatment on tumors by DCE-MRI with gadopentate.


Publication metadata

Author(s): Bradley DP, Tessier JT, Lacey T, Scott M, J├╝rgensmeier JM, Odedra R, Mills J, Kilburn L, Wedge SR

Publication type: Article

Publication status: Published

Journal: Magnetic Resonance Imaging

Year: 2009

Volume: 27

Issue: 3

Pages: 377-384

ISSN (print): 0730-725X

ISSN (electronic): 1873-5894

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.mri.2008.07.021

DOI: 10.1016/j.mri.2008.07.021


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