Robinson, SP and Kalber, TL and Howe, FA and McIntyre, DJO and Griffiths, JR and Blakey, DC and Whittaker, L and Ryan, AJ and Watertont, JC (2005) Acute tumor response to ZD6126 assessed by intrinsic susceptibility magnetic resonance imaging. NEOPLASIA , 7 (5) 466 - 474. 10.1593/neo.04622.
The effective magnetic resonance imaging (MRI) transverse relaxation rate R-2* was investigated as an early acute marker of the response of rat GH3 prolactinomas to the vascular-targeting agent, ZD6126. Multigradient echo (MGRE) MRI was used to quantify R-2*, which is sensitive to tissue deoxyhemoglobin levels. Tumor R-2* was measured prior to, and either immediately for up to 35 minutes, or 24 hours following administration of 50 mg/kg ZD6126. Following MRI, tumor perfusion was assessed by Hoechst 33342 uptake. Tumor R-2* significantly increased to 116 +/- 4% of baseline 35 minutes after challenge, consistent with an ischemic insult induced by vascular collapse. A strong positive correlation between baseline R-2* and the subsequent increase in R-2* measured 35 minutes after treatment was obtained, suggesting that the baseline R-2* is prognostic for the subsequent tumor response to ZD6126. In contrast, a significant decrease in tumor R-2* was found 24 hours after administration of ZD61126. Both the 35-minute and 24-hour R-2* responses to ZD6126 were associated with a decrease in Hoechst 33342 uptake. Interpretation of the R-2* response is complex, yet changes in tumor R-2* may provide a convenient and early MRI biomarker for detecting the antitumor activity of vascular-targeting agents.
|Title:||Acute tumor response to ZD6126 assessed by intrinsic susceptibility magnetic resonance imaging|
|Open access status:||An open access publication|
|Keywords:||ZD6126, vascular-targeting agents, MRI, tumor perfusion, response biomarker, VASCULAR-TARGETING AGENT, DIMETHYLARGININE DIMETHYLAMINOHYDROLASE, ANTIVASCULAR AGENT, COMBRETASTATIN A-4, MODEL SYSTEMS, BLOOD-FLOW, CANCER, ANGIOGENESIS, THERAPY, MRI|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics|
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