18F-FDG-PET/CT imaging of drug-induced metabolic changes in genetically engineered mouse lung cancer models.

The most commonly used radiotracer for cancer imaging in humans and mice is 2-deoxy-2-((18)F)fluoro-d-glucose ((18)F-FDG). We have used FDG coupled with positron-emission tomography (PET) to assess the pharmacodynamic efficacy of a number of therapeutics in genetically engineered mouse lung cancer models. In this protocol, we present our approach for FDG-PET imaging of early tumor metabolic changes induced by drug treatment. Special consideration is given to animal preparation, anesthesia, and PET/computed tomography (CT) imaging of mice with lung tumors. Specifically, we recommend fasting the mice overnight to reduce background, using sevoflurane anesthesia and a "conscious" uptake period to minimize cardiac FDG uptake, adopting a relatively short duration of CT and PET scanning to facilitate serial imaging, and quantifying the comparison between the maximum standardized uptake values (SUVs) of lung tumors before and after treatment to determine treatment effects. Used in this manner, FDG-PET can rapidly assess tumor metabolism before and after treatment with an experimental therapeutic. In many cases, metabolic changes are apparent after just a single dose of treatment, helping to show target engagement and modulation by the drug (pharmacodynamic efficacy) within days of starting therapy.