TY - JOUR
T1 - [18F]PI-2620 binding patterns in patients with suspected alzheimer disease and frontotemporal lobar degeneration
AU - Blazhenets, Ganna
AU - Soleimani-Meigooni, David N.
AU - Thomas, Wesley
AU - Mundada, Nidhi
AU - Brendel, Matthias
AU - Vento, Stephanie
AU - Vrede, Lawren Vande
AU - Heuer, Hilary W.
AU - Ljubenkov, Peter
AU - Rojas, Julio C.
AU - Chen, Miranda K.
AU - Amuiri, Alinda N.
AU - Miller, Zachary
AU - Gorno-Tempini, Maria L.
AU - Miller, Bruce L.
AU - Rosen, Howie J.
AU - Litvan, Irene
AU - Grossman, Murray
AU - Boeve, Brad
AU - Pantelyat, Alexander
AU - Tartaglia, Maria Carmela
AU - Irwin, David J.
AU - Dickerson, Brad C.
AU - Baker, Suzanne L.
AU - Boxer, Adam L.
AU - Rabinovici, Gil D.
AU - Joie, Renaud La
N1 - Publisher Copyright:
© 2023 Society of Nuclear Medicine Inc.. All rights reserved.
PY - 2023
Y1 - 2023
N2 - Tau PET has enabled the visualization of paired helical filaments of 3 or 4C-Terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18F]fluoro)-pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c9]dipyridine ([18F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [18F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-b (Ab) PET. Scans were acquired 30 60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30 40, 35 45, 50 60min). Age-and sex-Adjusted z score maps were computed for each patient, relative to 23 Ab-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Ab-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex predominant [18F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (r 5 0.53, P 5 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83 1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61 0.92] at 30 40min vs. 0.81 [95% CI, 0.66 0.96] at 50 60min; P 5 0.67). Conclusion: [18F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [18F]PI-2620 binding and the usefulness of [18F]PI2620 SUVr quantification outside the AD continuum.
AB - Tau PET has enabled the visualization of paired helical filaments of 3 or 4C-Terminal repeat tau in Alzheimer disease (AD), but its ability to detect aggregated tau in frontotemporal lobar degeneration (FTLD) spectrum disorders is uncertain. We investigated 2-(2-([18F]fluoro)-pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5c9]dipyridine ([18F]PI-2620), a newer tracer with ex vivo evidence for binding to FTLD tau, in a convenience sample of patients with suspected FTLD and AD using a static acquisition protocol and parametric SUV ratio (SUVr) images. Methods: We analyzed [18F]PI-2620 PET data from 65 patients with clinical diagnoses associated with AD or FTLD neuropathology; most (60/65) also had amyloid-b (Ab) PET. Scans were acquired 30 60 min after injection; SUVr maps (reference, inferior cerebellar cortex) were created for the full acquisition and for 10-min truncated sliding windows (30 40, 35 45, 50 60min). Age-and sex-Adjusted z score maps were computed for each patient, relative to 23 Ab-negative cognitively healthy controls (HC). Mean SUVr in the globus pallidus, substantia nigra, subthalamic nuclei, dentate nuclei, white matter, and temporal gray matter was extracted for the full and truncated windows. Results: Patients with suspected AD neuropathology (Ab-positive patients with mild cognitive impairment or AD dementia) showed high-intensity temporoparietal cortex predominant [18F]PI-2620 binding. At the group level, patients with clinical diagnoses associated with FTLD (progressive supranuclear palsy with Richardson syndrome [PSP Richardson syndrome], corticobasal syndrome, and nonfluent-variant primary progressive aphasia) exhibited higher globus pallidus SUVr than did HCs; pallidal retention was highest in the PSP Richardson syndrome group, in whom SUVr was correlated with symptom severity (r 5 0.53, P 5 0.05). At the individual level, only half of PSP Richardson syndrome, corticobasal syndrome, and nonfluent-variant primary progressive aphasia patients had a pallidal SUVr above that of HCs. Temporal SUVr discriminated AD patients from HCs with high accuracy (area under the receiver operating characteristic curve, 0.94 [95% CI, 0.83 1.00]) for all time windows, whereas discrimination between patients with PSP Richardson syndrome and HCs using pallidal SUVr was fair regardless of time window (area under the receiver operating characteristic curve, 0.77 [95% CI, 0.61 0.92] at 30 40min vs. 0.81 [95% CI, 0.66 0.96] at 50 60min; P 5 0.67). Conclusion: [18F]PI-2620 SUVr shows an intense and consistent signal in AD but lower-intensity, heterogeneous, and rapidly decreasing binding in patients with suspected FTLD. Further work is needed to delineate the substrate of [18F]PI-2620 binding and the usefulness of [18F]PI2620 SUVr quantification outside the AD continuum.
KW - Alzheimer disease
KW - FTLD
KW - PI2620
KW - Tau PET
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U2 - 10.2967/jnumed.123.265856
DO - 10.2967/jnumed.123.265856
M3 - Article
C2 - 37918868
AN - SCOPUS:85178651602
SN - 0161-5505
VL - 64
SP - 1980
EP - 1989
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 12
ER -