title: Molecular imaging of akt enables early prediction of response to molecular targeted therapy.
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.
authors.affiliation: Department of Radiation Oncology, University of Michigan Cancer Center, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mahaveer S
authors.initials: MS
authors.lastname: Bhojani
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Nyati
authors.forename: Lili
authors.initials: L
authors.lastname: Zhao
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Normolle
authors.forename: Brian D
authors.initials: BD
authors.lastname: Ross
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.forename: Alnawaz
authors.initials: A
authors.lastname: Rehemtulla