Molecular imaging of akt enables early prediction of response to molecular targeted therapy

Mahaveer S. Bhojani, Mukesh K. Nyati, Lili Zhao, Daniel P. Normolle, Brian D. Ross, Theodore S. Lawrence, Alnawaz Rehemtulla*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)122-125
Number of pages4
JournalTranslational Oncology
Volume4
Issue number3
DOIs
StatePublished - Jun 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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