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Head-to-head comparison of tau positron emission tomography tracers [18F]flortaucipir and [18F]RO948

Smith, Ruben LU ; Schöll, Michael LU ; Leuzy, Antoine LU ; Jögi, Jonas LU orcid ; Ohlsson, Tomas ; Strandberg, Olof LU and Hansson, Oskar LU orcid (2020) In European Journal of Nuclear Medicine and Molecular Imaging 47(2). p.342-354
Abstract

Purpose: [18F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [18F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [18F]flortaucipir with the novel tau tracer [18F]RO948 head-to-head in vivo. Methods: We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [18F]flortaucipir (80–100 min) and [18F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic... (More)

Purpose: [18F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [18F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [18F]flortaucipir with the novel tau tracer [18F]RO948 head-to-head in vivo. Methods: We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [18F]flortaucipir (80–100 min) and [18F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region. Results: Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [18F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [18F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [18F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [18F]flortaucipir SUVR over the scanning interval, compared with a plateau for [18F]RO948. Conclusion: [18F]RO948 and [18F]flortaucipir bound comparably in neocortical regions, but [18F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with [18F]RO948, compared with previous tau ligands.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Head-to-head, Neurodegeneration, PET, Tau
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
47
issue
2
pages
13 pages
publisher
Springer
external identifiers
  • pmid:31612245
  • scopus:85074480799
ISSN
1619-7070
DOI
10.1007/s00259-019-04496-0
language
English
LU publication?
yes
id
b189b738-4f28-403c-9f25-7e79f61ad996
date added to LUP
2019-11-21 14:01:11
date last changed
2022-06-14 00:51:07
@article{b189b738-4f28-403c-9f25-7e79f61ad996,
  abstract     = {{<p>Purpose: [<sup>18</sup>F]flortaucipir binds to paired helical filament tau and accurately identifies tau in Alzheimer’s disease (AD). However, “off-target” binding interferes with the quantification of [<sup>18</sup>F]flortaucipir in several brain regions. Recently, other tau PET tracers have been developed. Here, we compare [<sup>18</sup>F]flortaucipir with the novel tau tracer [<sup>18</sup>F]RO948 head-to-head in vivo. Methods: We included 18 participants with AD, three with amyloid-β-positive amnestic mild cognitive impairment, and four healthy controls. All underwent [<sup>18</sup>F]flortaucipir (80–100 min) and [<sup>18</sup>F]RO948 (70–90) PET scans within approximately 1 month. Four study participants underwent 0–100-min dynamic scanning. Standardized uptake value ratios (SUVRs) were created using an inferior cerebellar reference region. Results: Neocortical tracer retention was highly comparable using both SUVR and distribution volume ratio-1 values obtained from dynamic scans. However, [<sup>18</sup>F]RO948 retention was significantly higher in the entorhinal cortex and lower in the basal ganglia, thalamus, and choroid plexus compared with [<sup>18</sup>F]flortaucipir. Increased off-target binding was observed with age for both tracers. Several cases exhibited strong [<sup>18</sup>F]RO948 retention in the skull/meninges. This extra-cerebral signal, however, did not affect diagnostic accuracy and remained relatively unchanged when re-examining a subsample after 1 year. Kinetic modeling showed an increase in [<sup>18</sup>F]flortaucipir SUVR over the scanning interval, compared with a plateau for [<sup>18</sup>F]RO948. Conclusion: [<sup>18</sup>F]RO948 and [<sup>18</sup>F]flortaucipir bound comparably in neocortical regions, but [<sup>18</sup>F]RO948 showed higher retention in the medial temporal lobe and lower intracerebral “off-target” binding. Time-dependent bias of SUVR estimates may prove less of a factor with [<sup>18</sup>F]RO948, compared with previous tau ligands.</p>}},
  author       = {{Smith, Ruben and Schöll, Michael and Leuzy, Antoine and Jögi, Jonas and Ohlsson, Tomas and Strandberg, Olof and Hansson, Oskar}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Head-to-head; Neurodegeneration; PET; Tau}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{342--354}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Head-to-head comparison of tau positron emission tomography tracers [<sup>18</sup>F]flortaucipir and [<sup>18</sup>F]RO948}},
  url          = {{http://dx.doi.org/10.1007/s00259-019-04496-0}},
  doi          = {{10.1007/s00259-019-04496-0}},
  volume       = {{47}},
  year         = {{2020}},
}