Tieming Zhao

[18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer's disease

We wished to develop a highly selective positron emission tomography (PET) imaging agent targeting PHF‐tau in human Alzheimers disease (AD) brains.

A Highly Selective and Specific PET Tracer for Imaging of Tau Pathologies

Senile plaques and neurofibrillary tangles are prominent neuropathological hallmarks in Alzheimers disease and are considered to be targets for therapeutic intervention as well as biomarkers for diagnostic in vivo imaging agents. While there are a number of amyloid-β positron emission tomography (PET) tracers currently in different stages of clinical development and commercialization, there have been very few reports on imaging agents selectively targeting tau aggregates. In search of [18F]-PET tracers that possess great binding affinity and selectivity toward tau tangles, we tested more than 900 compounds utilizing a unique screening process. A competitive autoradiography assay was set up to test compounds for binding to native tau tangles and amyloid-β plaques on human brain tissue sections. In our in vitro assays, the 18F labeled compound [18F]-T808 displayed a high level of binding affinity and good selectivity for tau aggregates over amyloid-β plaques. [18F]-T808 showed rapid uptake and washout in rodent brains. Our in vitro and preclinical in vivo studies suggest that [18F]-T808 possesses suitable properties and characteristics to be a specific and selective PET probe for imaging of paired helical filament tau in human brains.

In Vitro and In Vivo Evaluation of the Caspase-3 Substrate-Based Radiotracer [ 18 F]-CP18 for PET Imaging of Apoptosis in Tumors

PurposeA novel caspase-3 substrate-based probe [18F]-CP18 was evaluated as an in vivo positron emission tomography (PET) imaging agent for monitoring apoptosis in tumors.MethodsUptake of [18F]-CP18 in cell assays and tumors was measured. Caspase-3/7 activities in cell lysates and tumor homogenates were determined. Autoradiography,Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and cleaved caspase-3 immunostaining were performed on adjacent tumor sections to identify areas of apoptosis.ResultsThe in vitro cell assays showed caspase-3-dependent uptake of [18F]-CP18 in tumor cells when treated with an apoptosis inducer. The in vivo microPET imaging signal of [18F]-CP18 in xenograft tumors correlated with the ex vivo caspase-3/7 activities in these tumors. Furthermore, tumor autoradiographies of [18F]-CP18 in tumor sections matched adjacent sections stained by TUNEL and caspase-3 immunohistochemistry (IHC).Conclusions[18F]-CP18 demonstrated high affinity and selectivity for activated caspase-3 both in vitro and in vivo, and the results support [18F]-CP18 as a promising new PET imaging agent for apoptosis.