Brain‐Wide Cellular‐Resolution Measurement of Antibody Therapeutic Biodistribution

Background To look deep inside tissues, traditional histological methods cut specimens into thin slices. Providing access to the intricate anatomy of intact organs, tissue clearing offers neuroscientists unbiased and complete views of brain anatomy and function. One area where these methods have particular utility is in the development of CNS therapeutics where they can be used to examine the regional distribution of the therapeutics in the brain as well as brain‐wide target engagement and phenotypic efficacy. We have developed a pipeline that provides unbiased and complete cellular resolution measurements of brain‐wide therapeutic biodistribution in pre‐clinical rodent brains. Methods With our optimized iDISCO‐based clearing method and our Mesoscale Imaging System for ZEISS Lightsheet microscopes, we can image cellular‐resolution immunoreactivity across entire mouse brains in