In Vivo Three-dimensional Brain Imaging with Chemiluminescence Probes in Alzheimer’s Disease Models

Abstract

AbstractOptical 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 (QY), relatively long emission wavelengths, and high signal-to-noise ratios (SNRs) 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 4×107photon/s/cm2/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 (AD).Significance StatementAlthough MRI, PET, CT, and SPECT have been routinely used for 3D imaging, including 3D brain imaging, they are considerably expensive. Optical imaging is largely low-cost and high throughput. However, the 3D capacity of optical imaging is always limited. Obviously, optical 3D molecular imaging is highly challenging, particularly for 3D brain imaging. In this report, we provided the first example of 3D brain imaging with chemiluminescence probes ADLumin-Xs, which have advantages in quantum yields (QY), emission wavelengths, and signal-to-noise ratios (SNRs) to fulfill the requirements for 3D brain imaging. And we believe that such 3D capacity is potentially a game-changer for brain molecular imaging in preclinical studies.