THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: A case report

Hee Jin Kim, Hanna Cho, Seongbeom Park, Hyemin Jang, Young Hoon Ryu, Jae Yong Choi, Seung Hwan Moon, Seung Jun Oh, Minyoung Oh, Duk L. Na, Chul Hyoung Lyoo, Eun Joo Kim, William W. Seeley, Jae Seung Kim, Kyung Chan Choi, Sang Won Seo

Research output: Contribution to journalArticle

Abstract

Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study. Case presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody. Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.

Original languageEnglish
Article number211
JournalBMC neurology
Volume19
Issue number1
DOIs
Publication statusPublished - 2019 Aug 29

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Creutzfeldt-Jakob Syndrome
Monoamine Oxidase
Occipital Lobe
Akinetic Mutism
Ligands
14-3-3 Proteins
Neurofibrillary Tangles
Gliosis
Astrocytes
Cerebrospinal Fluid
Dementia
Seizures
THK5351
Antibodies

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

Cite this

Kim, Hee Jin ; Cho, Hanna ; Park, Seongbeom ; Jang, Hyemin ; Ryu, Young Hoon ; Choi, Jae Yong ; Moon, Seung Hwan ; Oh, Seung Jun ; Oh, Minyoung ; Na, Duk L. ; Lyoo, Chul Hyoung ; Kim, Eun Joo ; Seeley, William W. ; Kim, Jae Seung ; Choi, Kyung Chan ; Seo, Sang Won. / THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient : A case report. In: BMC neurology. 2019 ; Vol. 19, No. 1.
@article{a129d886d2bc467eaf1b6474d8710759,
title = "THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: A case report",
abstract = "Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study. Case presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody. Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.",
author = "Kim, {Hee Jin} and Hanna Cho and Seongbeom Park and Hyemin Jang and Ryu, {Young Hoon} and Choi, {Jae Yong} and Moon, {Seung Hwan} and Oh, {Seung Jun} and Minyoung Oh and Na, {Duk L.} and Lyoo, {Chul Hyoung} and Kim, {Eun Joo} and Seeley, {William W.} and Kim, {Jae Seung} and Choi, {Kyung Chan} and Seo, {Sang Won}",
year = "2019",
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Kim, HJ, Cho, H, Park, S, Jang, H, Ryu, YH, Choi, JY, Moon, SH, Oh, SJ, Oh, M, Na, DL, Lyoo, CH, Kim, EJ, Seeley, WW, Kim, JS, Choi, KC & Seo, SW 2019, 'THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient: A case report', BMC neurology, vol. 19, no. 1, 211. https://doi.org/10.1186/s12883-019-1434-z

THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient : A case report. / Kim, Hee Jin; Cho, Hanna; Park, Seongbeom; Jang, Hyemin; Ryu, Young Hoon; Choi, Jae Yong; Moon, Seung Hwan; Oh, Seung Jun; Oh, Minyoung; Na, Duk L.; Lyoo, Chul Hyoung; Kim, Eun Joo; Seeley, William W.; Kim, Jae Seung; Choi, Kyung Chan; Seo, Sang Won.

In: BMC neurology, Vol. 19, No. 1, 211, 29.08.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - THK5351 and flortaucipir PET with pathological correlation in a Creutzfeldt-Jakob disease patient

T2 - A case report

AU - Kim, Hee Jin

AU - Cho, Hanna

AU - Park, Seongbeom

AU - Jang, Hyemin

AU - Ryu, Young Hoon

AU - Choi, Jae Yong

AU - Moon, Seung Hwan

AU - Oh, Seung Jun

AU - Oh, Minyoung

AU - Na, Duk L.

AU - Lyoo, Chul Hyoung

AU - Kim, Eun Joo

AU - Seeley, William W.

AU - Kim, Jae Seung

AU - Choi, Kyung Chan

AU - Seo, Sang Won

PY - 2019/8/29

Y1 - 2019/8/29

N2 - Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study. Case presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody. Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.

AB - Background: THK5351 and flortaucipir tau ligands have high affinity for paired helical filament tau, yet diverse off-target bindings have been reported. Recent data support the hypothesis that THK5351 binds to monoamine oxidase B (MAO-B) expressed from reactive astrocytes and that flortaucipir has an affinity toward MAO-A and B; however, pathological evidence is lacking. We performed a head-to-head comparison of the two tau ligands in a sporadic Creutzfeldt-Jakob disease (CJD) patient and performed an imaging-pathological correlation study. Case presentation: A 67-year-old man visited our clinic a history of 6 months of rapidly progressive dementia, visual disturbance, and akinetic mutism. Diffusion-weighted imaging showed cortical diffusion restrictions in the left temporo-parieto-occipital regions. 18F-THK5351 PET, but not 18F-flortaucipir PET showed high uptake in the left temporo-parieto-occipital regions, largely overlapping with the diffusion restricted areas. Cerebrospinal fluid analysis was weakly positive for 14-3-3 protein and pathogenic prion protein was found. The patient showed rapid cognitive decline along with myoclonic seizures and died 13 months after his first visit. A post-mortem study revealed immunoreactivity for PrPsc, no evidence of neurofibrillary tangles, and abundant astrocytosis which was reactive for MAO-B antibody. Conclusions: Our findings add pathological evidence that increased THK5351 uptake in sporadic CJD patients might be caused by an off-target binding driven by its high affinity for MAO-B.

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UR - http://www.scopus.com/inward/citedby.url?scp=85071628425&partnerID=8YFLogxK

U2 - 10.1186/s12883-019-1434-z

DO - 10.1186/s12883-019-1434-z

M3 - Article

C2 - 31464590

AN - SCOPUS:85071628425

VL - 19

JO - BMC Neurology

JF - BMC Neurology

SN - 1471-2377

IS - 1

M1 - 211

ER -