Journal of Alzheimer's Disease
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Home > S-[18F]THK-5117-PET and [11C]PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-β Plaques and Tau in Brain Biopsies.

TitleS-[18F]THK-5117-PET and [11C]PIB-PET Imaging in Idiopathic Normal Pressure Hydrocephalus in Relation to Confirmed Amyloid-β Plaques and Tau in Brain Biopsies.
Publication TypeJournal Article
Year of Publication2018
AuthorsLeinonen, V, Rauramaa, T, Johansson, J, Bottelbergs, A, Tesseur, I, van der Ark, P, Pemberton, D, Koivisto, AM, Jääskeläinen, JE, Hiltunen, M, Herukka, S-K, Blennow, K, Zetterberg, H, Jokinen, P, Rokka, J, Helin, S, Haaparanta-Solin, M, Solin, O, Okamura, N, Kolb, HC, Rinne, JO
JournalJ Alzheimers Dis
Volume64
Issue1
Pagination171-179
Date Published2018
ISSN1875-8908
Abstract

BACKGROUND: Detection of pathological tau aggregates could facilitate clinical diagnosis of Alzheimer's disease (AD) and monitor drug effects in clinical trials. S-[18F]THK-5117 could be a potential tracer to detect pathological tau deposits in brain. However, no previous study have correlated S-[18F]THK-5117 uptake in PET with brain biopsy verified tau pathology in vivo.

OBJECTIVE: Here we aim to evaluate the association between cerebrospinal fluid (CSF) AD biomarkers, S-[18F]THK-5117, and [11C]PIB PET against tau and amyloid lesions in brain biopsy.

METHODS: Fourteen patients with idiopathic normal pressure hydrocephalus (iNPH) with previous shunt surgery including right frontal cortical brain biopsy and CSF Aβ1 - 42, total tau, and P-tau181 measures, underwent brain MRI, [11C]PIB PET, and S-[18F]THK-5117 PET imaging.

RESULTS: Seven patients had amyloid-β (Aβ, 4G8) plaques, two both Aβ and phosphorylated tau (Pτ, AT8) and one only Pτ in biopsy. As expected, increased brain biopsy Aβ was well associated with higher [11C]PIB uptake in PET. However, S-[18F]THK-5117 uptake did not show any statistically significant correlation with either brain biopsy Pτ or CSF P-tau181 or total tau.

CONCLUSIONS: S-[18F]THK-5117 lacked clear association with neuropathologically verified tau pathology in brain biopsy probably, at least partially, due to off-target binding. Further studies with larger samples of patients with different tau tracers are urgently needed. The detection of simultaneous Aβ and tau pathology in iNPH is important since that may indicate poorer and especially shorter response for CSF shunt surgery compared with no pathology.

DOI10.3233/JAD-180071
Alternate JournalJ. Alzheimers Dis.
PubMed ID29865068
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Source URL: https://www.j-alz.com/content/s-18fthk-5117-pet-and-11cpib-pet-imaging-idiopathic-normal-pressure-hydrocephalus-relation