RT Journal Article
SR Electronic
T1 Comparison of regional flortaucipir PET SUVr values to quantitative tau histology and quantitative tau immunoassay in patients with Alzheimer’s disease pathology: A clinico-pathological study
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 629
OP 629
VO 58
IS supplement 1
A1 Siderowf, Andrew
A1 Keene, C.
A1 Beach, Thomas
A1 Montine, Thomas
A1 Arora, Anupa
A1 Devous, Michael
A1 Navitsky, Michael
A1 Kennedy, Ian
A1 Joshi, Abhinay
A1 Pontecorvo, Michael
A1 Lu, Ming
A1 Serrano, Geidy
A1 Rose, Shannon
A1 Wilson, Angela
A1 Hellstern, Leanne
A1 Coleman, Natalie
A1 Mintun, Mark
YR 2017
UL http://jnm.snmjournals.org/content/58/supplement_1/629.abstract
AB 629Objectives: PET tracers for tau pathology in Alzheimer’s disease (AD) are of increasing interest as diagnostics and as markers of disease severity. However, there have been few studies validating tau PET imaging relative to the standard of pathological assessment at autopsy. The objective of this study was to make a quantitative comparison of 18F-flortaucipir (F18-AV-1451) PET uptake across a range of brain regions obtained in end-of-life subjects to density of tau pathology observed at autopsy in these same regions.Methods: Patients at end-of-life were recruited for this pilot phase of a pivotal clinical trial. Participants had PET imaging consisting of an injection of ~370 mBq flortaucipir F18 followed by imaging from 80-100 minutes after injection. After death, blocks of brain tissue from representative neocortical and limbic regions were obtained for assessment of the density and extent of tau pathology. Subject-specific PET regions of interest corresponding to pathology blocks were constructed for 14 regions in each hemisphere (28 regions per subject). Regions were hand drawn on the PET images of each subject using photographs of the gross pathology blocks to identify the corresponding anatomy on the PET scan. SUVr values were calculated using a cerebellar reference region. Tau pathology was assessed using a quantitative antibody capture assay (Histelide) designed for paraffin-embedded tissue using the AT8 phospho-tau antibody (Postupna et al; Brain Pathol. 2012). All image and pathology assessments were conducted blinded relative to the other measure.Results: 3 participants with a clinical diagnosis of Alzheimer’s disease were included in this study. The intervals between imaging and death for the three cases were 4, 12 and 27 days. Two cases were found to be Braak stage 5 at autopsy and one was Braak stage 6, but examination of individual tissue blocks showed that tau pathology ranged from absent in some blocks to frequent others. Regional SUVr values ranged from 1.02 to 2.60 and quantitative immunoassay values, normalized to gray matter (GM) area, ranged from -0.51 to 83.01 ug p-nitrophenol/cm2 of GM. There was a highly significant correlation across all patients between regional SUVr and quantitative tau immunoassay (pearson r = 0.81; p<0.0001). There was also a highly significant correlation between regional flortaucipir SUVr and tau immunoassay for each individual case (r = 0.54; 0.73; 0.75; p<0.005 for all).Conclusion: The results of this pilot study support a quantitative relationship between flortaucipir SUVr values and quantitative measures of tau pathology at autopsy. Additional research including more cases are needed to confirm the generalizability of these results. Research Support: This study was supported by Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company.