In vivo three-dimensional brain imaging with chemiluminescence probes in Alzheimer’s disease models
Jing Zhang, Carly Wickizer, Weihua Ding, Richard Van, Liuyue Yang, Biyue Zhu, Jun Yang, Yanli Wang, Yongle Wang, Yulong Xu, Can Zhang, Shiqian Shen, Changning Wang, Yihan Shao, Chongzhao Ran
Abstract
Optical three-dimensional (3D) molecular imaging is highly desirable for providing precise distribution of the target-of-interest in disease models. However, such 3D imaging is still far from wide applications in biomedical research; 3D brain optical molecular imaging, in particular, has rarely been reported. In this report, we designed chemiluminescence probes with high quantum yields, relatively long emission wavelengths, and high signal-to-noise ratios to fulfill the requirements for 3D brain imaging in vivo. With assistance from density-function theory (DFT) computation, we designed ADLumin-Xs by locking up the rotation of the double bond via fusing the furan ring to the phenyl ring. Our results showed that ADLumin-5 had a high quantum yield of chemiluminescence and could bind to amyloid beta (Aβ). Remarkably, ADLumin-5’s radiance intensity in brain areas could reach 4 × 10 7 photon/s/cm 2 /sr, which is probably 100-fold higher than most chemiluminescence probes for in vivo imaging. Because of its strong emission, we demonstrated that ADLumin-5 could be used for in vivo 3D brain imaging in transgenic mouse models of Alzheimer’s disease.