This research plan aims at developing an innovative platform of PET and SPECT imaging agents that concomitantly target indoleamine 2,3-dioxygenase 1/2 (IDO1/IDO2) and tryptophan 2,3-dioxygenase (TDO), three enzymes that play a crucial role in tumor biology. In particular, the enhanced tryptophan catabolism mediated by activation of these enzymes in many human cancers, was recently shown to be fundamental in the ability of tumors to breach the defense mechanisms of the immune system leading to cancer establishment and progression. Since these enzymes are not over-expressed in all malignancies, the novel imaging agents could represent a step-change in our ability to improve diagnosis, enhance personalized medicine, monitor the response to immunomodulating therapies and unravel the complicated scenery of immunomodulation.