Effect of IGF-1R inhibitor BMS-754807 on tumor glucose metabolism and proliferation in Sal-IGF xenografts by FDG and FLT- PET imaging

e14501 Background: The type 1 insulin-like growth factor receptor (IGF-1R) plays a critical role in mitogenesis and survival in a variety of human tumor cells. IGF-1R is also closely related to the insulin receptor (IR). It is becoming increasingly evident that stimulation of IR or IR/IGF-1R hybrid receptors by insulin or IGF-1/2 may contribute to cancer growth, suggesting that both IGF-1R and IR may be targets for cancer therapy. BMS-754807 (‘807) is an oral IGF-1R tyrosine kinase antagonist under development that also blocks IR activity. This study explores the feasibility of fluorodeoxyglucose (FDG) and fluorothymidine (FLT) positron emission tomography (PET) as pharmacodynamic imaging biomarkers in a xenograft model. Methods: Mice were implanted with fragments of Sal-IGF, a transgenic salivary gland tumor expressing constitutively active IGF-1R. Once tumors reached desired size, the mice were divided into 3 treatment groups (vehicle, 6.25 mg/kg ‘807, & 50 mg/kg ‘807 on days 1–4). FDG-PET scans were pe...