TY - JOUR
T1 - Molecular imaging of akt enables early prediction of response to molecular targeted therapy
AU - Bhojani, Mahaveer S.
AU - Nyati, Mukesh K.
AU - Zhao, Lili
AU - Normolle, Daniel P.
AU - Ross, Brian D.
AU - Lawrence, Theodore S.
AU - Rehemtulla, Alnawaz
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
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U2 - 10.1593/tlo.11112
DO - 10.1593/tlo.11112
M3 - Article
C2 - 21633667
AN - SCOPUS:79957921255
SN - 1944-7124
VL - 4
SP - 122
EP - 125
JO - Translational Oncology
JF - Translational Oncology
IS - 3
ER -