Acute tumor response to ZD6126 assessed by intrinsic susceptibility magnetic resonance imaging.
Robinson SP., Kalber TL., Howe FA., McIntyre DJO., Griffiths JR., Blakey DC., Whittaker L., Ryan AJ., Waterton JC.
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.