RT Journal Article
SR Electronic
T1 Investigating Tau and Amyloid Tracer Skull Binding in Studies of Alzheimer Disease
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 287
OP 293
DO 10.2967/jnumed.122.263948
VO 64
IS 2
A1 Shaney Flores
A1 Charles D. Chen
A1 Yi Su
A1 Aylin Dincer
A1 Sarah J. Keefe
A1 Nicole S. McKay
A1 Angela M. Paulick
A1 Gloria Guzman Perez-Carrillo
A1 Liang Wang
A1 Russ C. Hornbeck
A1 Manu Goyal
A1 Andrei Vlassenko
A1 Sally Schwarz
A1 Michael L. Nickels
A1 Dean F. Wong
A1 Zhude Tu
A1 Jonathan E. McConathy
A1 John C. Morris
A1 Tammie L.S. Benzinger
A1 Brian A. Gordon
YR 2023
UL http://jnm.snmjournals.org/content/64/2/287.abstract
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.