Early Changes in [¹⁸F]FDG Uptake as a Readout for PI3K/Akt/mTOR Targeted Drugs in HER-2-Positive Cancer Xenografts

Figure 1

Schematic overview of the regulation of glucose metabolism by the PI3K/Akt/mTOR pathway. The PI3K pathway is initiated when a growth factor like HER-2 binds its receptor. PI3K then catalyzes the phosphorylation of phosphatidylinositol biphosphatase (PIP2) to phosphatidylinositol triphosphatase (PIP3). PIP3 recruits and activates Akt. Thereafter, phosphorylated Akt stimulates mTOR. In the cell, Akt stimulates HK; as a consequence, glucose and [¹⁸F]FDG are phosphorylated at a higher rate. mTOR has an effect on the glucose metabolism through upregulation of the expression of GLUT1. Trastuzumab is an anti-HER-2 humanized monoclonal antibody. PIK90 is a PI3K inhibitor and everolimus is an mTOR inhibitor.