PT  - JOURNAL ARTICLE
AU  - Shaney Flores
AU  - Charles D. Chen
AU  - Yi Su
AU  - Aylin Dincer
AU  - Sarah J. Keefe
AU  - Nicole S. McKay
AU  - Angela M. Paulick
AU  - Gloria Guzman Perez-Carrillo
AU  - Liang Wang
AU  - Russ C. Hornbeck
AU  - Manu Goyal
AU  - Andrei Vlassenko
AU  - Sally Schwarz
AU  - Michael L. Nickels
AU  - Dean F. Wong
AU  - Zhude Tu
AU  - Jonathan E. McConathy
AU  - John C. Morris
AU  - Tammie L.S. Benzinger
AU  - Brian A. Gordon
TI  - Investigating Tau and Amyloid Tracer Skull Binding in Studies of Alzheimer Disease
AID  - 10.2967/jnumed.122.263948
DP  - 2023 Feb 01
TA  - Journal of Nuclear Medicine
PG  - 287--293
VI  - 64
IP  - 2
4099  - http://jnm.snmjournals.org/content/64/2/287.short
4100  - http://jnm.snmjournals.org/content/64/2/287.full
SO  - J Nucl Med2023 Feb 01; 64
AB  - Off-target binding of [18F]flortaucipir (FTP) can complicate quantitative PET analyses. An underdiscussed off-target region is the skull. Here, we characterize how often FTP skull binding occurs, its influence on estimates of Alzheimer disease pathology, its potential drivers, and whether skull uptake is a stable feature across time and tracers. Methods: In 313 cognitively normal and mildly impaired participants, CT scans were used to define a skull mask. This mask was used to quantify FTP skull uptake. Skull uptake of the amyloid-β PET tracers [18F]florbetapir and [11C]Pittsburgh compound B (n = 152) was also assessed. Gaussian mixture modeling defined abnormal levels of skull binding for each tracer. We examined the relationship of continuous bone uptake to known off-target binding in the basal ganglia and choroid plexus as well as skull density measured from the CT. Finally, we examined the confounding effect of skull binding on pathologic quantification. Results: We found that 50 of 313 (∼16%) FTP scans had high levels of skull signal. Most were female (n = 41, 82%), and in women, lower skull density was related to higher FTP skull signal. Visual reads by a neuroradiologist revealed a significant relationship with hyperostosis; however, only 21% of women with high skull binding were diagnosed with hyperostosis. FTP skull signal did not substantially correlate with other known off-target regions. Skull uptake was consistent over longitudinal FTP scans and across tracers. In amyloid-β–negative, but not –positive, individuals, FTP skull binding impacted quantitative estimates in temporal regions. Conclusion: FTP skull binding is a stable, participant-specific phenomenon and is unrelated to known off-target regions. Effects were found primarily in women and were partially related to lower bone density. The presence of [11C]Pittsburgh compound B skull binding suggests that defluorination does not fully explain FTP skull signal. As signal in skull bone can impact quantitative analyses and differs across sex, it should be explicitly addressed in studies of aging and Alzheimer disease.