Acute tumor response to ZD6126 assessed by intrinsic susceptibility magnetic resonance imaging.
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| Abstract |
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 ZD6126. 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.
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| Authors | Simon P Robinson, Tammy L Kalber, Franklyn A Howe, Dominick J O McIntyre, John R Griffiths, David C Blakey, Lynsey Whittaker, Anderson J Ryan, John C Waterton |
| Journal | Neoplasia (New York, N.Y.) (Neoplasia) Vol. 7 Issue 5 Pg. 466-74 (May 2005) ISSN: 1522-8002 [Print] United States |
| PMID | 15967099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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