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

Mahaveer S Bhojani1, Mukesh K Nyati, Lili Zhao

  • 1Department of Radiation Oncology, University of Michigan Cancer Center, University of Michigan, Ann Arbor, MI, USA.

Insights

Molecular imaging of Akt activity can predict tumor response to gemcitabine and cetuximab therapy earlier than traditional tumor volume measurements. This approach aids in optimizing individualized cancer treatment strategies.

Area of Science:

  • Oncology
  • Molecular Imaging
  • Cancer Therapy

Background:

  • Individualized therapy requires real-time tools to assess treatment response.
  • Molecular imaging sensors for Akt and caspase-3 activity have been previously developed.

Purpose of the Study:

  • To evaluate the utility of Akt and caspase-3 molecular imaging reporters in assessing tumor responsiveness to a combination therapy.
  • To compare two different administration schedules of gemcitabine and cetuximab in human head and neck cancer xenografts.

Main Methods:

  • Utilized noninvasive molecular imaging sensors for Akt and caspase-3 activity.
  • Administered combination therapy of gemcitabine (Gem) and cetuximab (Cet) in two distinct schedules.
  • Monitored tumor volumes and molecular reporter activity over time.
  • Employed Wilcoxon two-sample tests for statistical analysis.

Main Results:

  • Human head and neck cancer xenografts showed significantly better response when cetuximab was administered after gemcitabine.
  • Differences in tumor volume between schedules became significant on day 7.
  • Differences in Akt activity became significant on day 4, preceding tumor volume changes.
  • Molecular imaging of Akt activity allowed for earlier detection of therapy response (2 days prior to tumor volume).
  • No significant difference in caspase-3 activity was observed between the schedules.

Conclusions:

  • Molecular imaging of Akt activity can serve as an early indicator of therapeutic efficacy.
  • This study provides a proof-of-concept for using Akt imaging to predict treatment response in head and neck cancer.
  • Optimizing drug administration schedules is crucial for effective cancer therapy.