Owing to its ability to detect specific interactions in living mice, the BRET6 system provides a valuable platform to monitor PPIs in their native environment. The red-shifted BRET6 sensor can potentially be translated to study PPIs in other cancer models in small animals, especially in mice. Our BRET6 sensor could also be used for BRET imaging in highly vascularized tissues such as the liver; however, further optimization of the reporter's brightness in the desired cells expressing the BRET sensor may be needed to balance for the higher tissue attenuation in the liver. If necessary, wider (50-nm) donor/acceptor bandpass emission filters can be used to increase the signal output.