Medical Physics Seminar – Monday, October 10, 2022
Chemiluminescence and bioluminescence imaging of amyloid beta species of Alzheimer's disease
Chongzhao Ran, PhD
Associate Professor of Radiology, A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School
The number of preclinical and clinical drug candidates for Alzheimer's disease (AD) is dwarfed by cancer drugs at similar stages, by a factor of 100. One important contributor for this dire situation is the lack of reliable, low-cost, and efficient tools to assess treatment endpoints and disease progression in AD models.
Over the past decades, our research has been focusing on development cost-efficient optical imaging methods for reporting the level of Amyloid beta in preclinical animal models. We have demonstrated that CRANAD-Xs, a series of near infrared fluorescence (NIRF) probes created in my group, could be used to monitor the progress of AD and the efficiency of therapeutics in AD mouse models. In this talk, I will present our recent progress on Amyloid beta probe development. Specifically, I will show our results on developing chemiluminescence probes for Amyloid betas. Our preliminary results revealed that ADLumin-1 could be turned-on upon mixing with Amyloid beta. Notably, this chemiluminescence turn-on is not ROS-dependent, which is different from most of chemiluminescence probes.
In preclinical cancer research, bioluminescence imaging has been daily used in thousands of labs. However, utilizing bioluminescence imaging for AD research represents an "impossible" mission, due to the untaggability of amyloid beta and tau species with luciferase, the enzyme for bioluminescence whose size is much larger than that of Amyloid beta. In this study, we innovatively circumvent the untaggability problem via utilizing amyloid plaques as a reservoir, and we termed our method as "BLIAR" (bioluminescence imaging with amyloid reservoir). Through in vitro and in vivo studies, we validated that BLIAR could faithfully report the levels of amyloid beta in AD models. This represents a breakthrough imaging method that is compatible with in vivo assessment of the changes of amyloid beta. We believe that our approaches can be easily implemented into daily imaging experiments to accelerate AD drug discovery.