Molecular Imaging of Akt Enables Early Prediction of Response to Molecular Targeted Therapy

被引:7
|
作者
Bhojani, Mahaveer S. [1 ]
Nyati, Mukesh K. [1 ]
Zhao, Lili [2 ]
Normolle, Daniel P. [2 ]
Ross, Brian D. [3 ]
Lawrence, Theodore S. [1 ]
Rehemtulla, Alnawaz [1 ,4 ]
机构
[1] Univ Michigan, Dept Radiat Oncol, Univ Michigan Canc Ctr, Ann Arbor, MI 48109 USA
[2] Univ Michigan, Dept Biostat Unit, Univ Michigan Canc Ctr, Ann Arbor, MI 48109 USA
[3] Univ Michigan, Dept Radiol, Univ Michigan Canc Ctr, Ann Arbor, MI 48109 USA
[4] Univ Michigan, Ctr Mol Imaging, Univ Michigan Canc Ctr, Ann Arbor, MI 48109 USA
来源
TRANSLATIONAL ONCOLOGY | 2011年 / 4卷 / 03期
关键词
KINASES; CANCER; HEAD;
D O I
10.1593/tlo.11112
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Development of noninvasive, real-time molecular imaging tools to assess responsiveness of a given therapy may be a critical component of the success of individualized therapy approach for patients. Toward this, we have previously developed and validated molecular sensors for Akt and caspase-3 activity, and in this report, we have explored the utility of these reporters in assessing the responsiveness of tumors to a combination of gemcitabine (Gem) and cetuximab (Cet) delivered in two opposite schedules. We found that human head and neck cancer (UMSCC1) xenografts responded significantly better in a schedule where cetuximab was administered after gemcitabine when compared with the schedule of cetuximab followed by gemcitabine. Wilcoxon two-sample tests suggested that the difference in tumor volumes in two schedules became significant on day 7 (P > .05 on day 4, and P < .05 on days 7 and 10), and the difference in activity of Akt in two schedules became significant on day 4 (P < .05 on days 4, 6, and 10). Using Akt reporter activity and cubic spline interpolation, the distinction between the two schedules could be detected 2 days before using the tumor volume, suggesting that molecular imaging of Akt may allow early prediction of therapy responsiveness. We did not observe a significant difference between the two schedules in the caspase-3 activity. In summary, this proof-of-concept study provides a basis for using molecular imaging of Akt as an early indicator of therapeutic efficacy. Translational Oncology (2011) 4, 122-125
引用
收藏
页码:122 / U79
页数:5
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