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Record W4210327457 · doi:10.1002/1873-3468.14303

Improved synthesis of an ergothioneine PET radioligand for imaging oxidative stress in Alzheimer’s disease

2022· article· en· W4210327457 on OpenAlexaff
William J. Behof, Clayton A. Whitmore, Justin R. Haynes, Adam J. Rosenberg, Mohammed Noor Tantawy, Todd E. Peterson, Fiona E. Harrison, Robert B. Beelman, Printha Wijesinghe, Joanne A. Matsubara, Wellington Pham

Bibliographic record

VenueFEBS Letters · 2022
Typearticle
Languageen
FieldMedicine
TopicCholinesterase and Neurodegenerative Diseases
Canadian institutionsUniversity of British Columbia
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute on AgingNational Institutes of Health
KeywordsRadioligandErgothioneineOxidative stressChemistryIn vivoBiodistributionPharmacologyRadiosynthesisBiochemistryAntioxidantMedicineIn vitroBiology

Abstract

fetched live from OpenAlex

L‐ergothioneine (ERGO) is a potent antioxidant with cytoprotective effects. To study ERGO biodistribution and detect oxidative stress in vivo , we report an efficient and reproducible preparation of [ 11 C]‐labeled ERGO PET radioligand based on protecting the histidine carboxylic group with a methyl ester. Overall, this new protection approach using methyl ester improved the chemical yield of a 4‐step reaction from 14% to 24% compared to the previous report using t ‐butyl ester. The [ 11 C]CH 3 methylation of the precursor provided the desired product with 55 ± 10% radiochemical purity and a molar activity of 450 ± 200 TBq·mmol −1 . The [ 11 C]ERGO radioligand was able to detect threshold levels of oxidative stress in a preclinical animal model of Alzheimer’s disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.064
Threshold uncertainty score0.576

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.282
Teacher spread0.263 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations8
Published2022
Admission routes1
Has abstractyes

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