Correlation of 18F-PM-PBB3 (18F-florzolotau) Tau PET Imaging with Postmortem Neuropathological Findings in A Case with Progressive Supranuclear Palsy (P9-11.015)

Abstract

<h3>Objective:</h3> To examine correlations between <i>in vivo</i> positron emission tomography (PET) imaging with 18F-PM-PBB3 (18F-florzolotau) and postmortem neuropathological findings in a patient with progressive supranuclear palsy (PSP). <h3>Background:</h3> There have been no reports demonstrating tight PET-pathology associations in the same individual with non-Alzheimer-type neurodegenerative disorders, including PSP, characterized by aggregations of four-repeat tau isoforms only. 18F-florzolotau is a PET probe allowing high-contrast imaging of Alzheimer’s and non-Alzheimer tau pathologies irrespective of isoform compositions, while the utility of this tracer for quantifying the abundance of tau deposits in living cases is yet to be verified. <h3>Design/Methods:</h3> <h3>Patient:</h3> A 65-year-old male with a clinical diagnosis of PSP Richardson syndrome underwent 11C-PiB amyloid and 18F-florzolotau tau PET scans one year before autopsy. Clinical, neuroimaging, and neuropathological findings in this case were briefly summarized elsewhere (K Tagai, et al. Neuron 2021). <h3>Image analysis:</h3> The standardized uptake value ratio (SUVR) image was generated from averaged PET images at 90–110 min after injecting 18F-florzolotau. The reference region was determined using an optimized reference tissue method (K Tagai, et al. medRxiv DOI: https://doi.org/10.1101/2022.02.13.22270135). <h3>Neuropathological analysis:</h3> Quantitative analysis of tau burden was performed using an anti-phosphorylated tau antibody (AT8). A threshold-based binarization method was used for determining the mean AT-8-positive area (%area tau burden). <h3>Results:</h3> 18F-florzolotau PET showed enhanced radiosignals in the brainstem, subthalamic nucleus, and basal ganglia, and the presence of PSP-characteristic tau deposits, including the globose neurofibrillary tangle, tufted astrocytes and coiled bodies, primarily in these areas was confirmed by neuropathological assays. There was a close correlation between regional radioprobe SUVR and %area tau burden (<i>r</i><i>_s</i> = 0.63, <i>p</i> &lt;0.0001). Amyloid PET was negative by visual read. <h3>Conclusions:</h3> 18F-florzolotau PET measures reflect the abundance of tau pathologies in PSP. <b>Disclosure:</b> Dr. Endo has received personal compensation in the range of $500-$4,999 for serving as a Consultant for APRINOIA Therapeutics. Dr. Endo has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AbbVie Inc.. The institution of Dr. Endo has received research support from JSPS KAKENHI 21K15705. Dr. Araki has nothing to disclose. Dr. Takeda has nothing to disclose. Dr. Takado has nothing to disclose. Dr. Tagai has nothing to disclose. Dr. Matsuoka has nothing to disclose. Dr. Seki has nothing to disclose. Dr. Takahata has nothing to disclose. Dr. Sahara has nothing to disclose. Hitoshi Shinotoh has nothing to disclose. Mr. Kawamura has nothing to disclose. Dr. Zhang has nothing to disclose. Dr. Honda has nothing to disclose. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Guidepoint. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for eli lilly. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Takeda Pharmaceutical . Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Eisai. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Nihon Medi-Physics. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for FUJIFILM Toyama Chemical. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sunplanet . Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for NIPPON CHEMIPHAR. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sumitomo Pharma. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for GE Healthcare. Prof. SHIMADA has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for CHUGAI PHARMACEUTICAL. Prof. SHIMADA has received intellectual property interests from a discovery or technology relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. Prof. SHIMADA has received publishing royalties from a publication relating to health care. The institution of Dr. Higuchi has received research support from APRINOIA Therapeutics.